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Abstract Metallurgical slag such as solid waste generated in the steel industry carries environmental pollution risks, but it is rich in nutrients required by microalgae. Metallurgical slag used for carbon capture and biomass energy conversion has multiple benefits: (i) reduction and harmless treatment of metallurgical solid waste, (ii) assisting in carbon neutrality by efficient carbon fixation, and (iii) production of biodiesel from CO2. In this study, AOD, BOF, BFS, HVS, and VTS slag were applied to culture Chlorella pyrenoidosa (C. pyrenoidosa) with the regulation of growth, carbon fixation, and lipid synthesis. An excellent fixed amount of CO2 with 94.59 mg is obtained from C. pyrenoidosa biomass at BOF slag added (mass ratio of CO2 captured/microalgae/slag with 1.99/1.00/10.53) since high Ca/Mg mass ratio of 419 (8.38 mg/L Ca and 0.02 mg/L Mg), no Cr and low concentration of Al (0.04 mg/L) contribute to regulating antioxidant enzyme activity (SOD and POD) to resist ROS and improving PEPC activity to reduce carbon flux toward lipid to promote biomass synthesis. Both metal concentrations from Ca (5.86 mg/L), Mg (0.05 mg/L), Al (0.42 mg/L), and Cr (0.006 mg/L) and suitable pH (10.53) in AOD leaching solution at solid/liquid ratio of 0.5 g/L change carbon flow toward efficient lipid synthesis (47.07 wt%) by continuously providing raw materials and energy by regulating ACC, ME, and PEPC activities. High value‐added biodiesel with high concentrations of C16 and C18 methyl esters from lipid of C. pyrenoidosa is achieved, following other ecological and economic benefits including 197 mg CO2 captured and 2198 mg AOD applied with harmless. In this study, C. pyrenoidosa is cultured with elements from metallurgical slag solid waste, which promotes C. pyrenoidosa efficient carbon fixation to assist in carbon neutrality, and provides guidance for CO2 conversion to high‐value‐added products with low cost.

BackgroundInitial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections.Case summaryIn this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid.ConclusionAlthough contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.

Abstract Pullulanase is a well-known debranching enzyme that can specifically hydrolyze α-1,6-glycosidic linkages in starch and oligosaccharides, however, it suffers from low stability and catalytic efficiency under industrial conditions. In the present study, four residues (A365, V401, H499, and T504) lining the catalytic pocket of Anoxybacillus sp. AR-29 pullulanase (PulAR) were selected for site-directed mutagenesis (SDM) by using a structure-guided consensus approach. Five beneficial mutants (PulAR-A365V, PulAR-V401C, PulAR-A365/V401C, PulAR-A365V/V401C/T504V, and PulAR-A365V/V401C/T504V/H499A) were created, which showed enhanced thermostability, pH stability, and catalytic efficiency. Among them, the quadruple mutant PulAR-A365V/V401C/T504V/H499A displayed 6.6- and 9.6-fold higher catalytic efficiency toward pullulan at 60 ℃, pH 6.0 and 5.0, respectively. In addition, its thermostabilities at 60 ℃ and 65 ℃ were improved by 2.6- and 3.1-fold, respectively, compared to those of the wild-type (WT). Meanwhile, its pH stabilities at pH 4.5 and 5.0 were 1.6- and 1.8-fold higher than those of WT, respectively. In summary, the catalytic performance of PulAR was significantly enhanced by a structure-guided consensus approach. The resultant quadruple mutant PulAR-A365V/V401C/T504V/H499A demonstrated potential applications in the starch industry. Graphical Abstract

IntroductionThe Camellia oleifera (C. oleifera) cultivars 'Huashuo' (HS) and 'Huaxin' (HX) are new high-yielding and economically valuable cultivars that frequently encounter prolonged cold weather during the flowering period, resulting in decreased yields and quality. The flower buds of HS sometimes fail to open or open incompletely under cold stress, whereas the flower buds of HX exhibit delayed opening but the flowers and fruits rarely drop.MethodsIn this study, flower buds at the same development stage of two C. oleifera cultivars were used as test materials for a combination of physiological, transcriptomic and metabolomic analyses, to unravel the different cold regulatory mechanisms between two cultivars of C. oleifera.Results and discussionKey differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) involved in sugar metabolism, phenylpropanoid biosynthesis, and hormone signal transduction were significantly higher in HX than in HS, which is consistent with phenotypic observations from a previous study. The results indicate that the flower buds of HX are less affected by long-term cold stress than those of HS, and that cold resistance in C. oleifera cultivars varies among tissues or organs.This study will provide a basis for molecular markers and molecular breeding of C. oleifera.

Cao, Li, et al. sequence 13 perennial woody plant species of Lycium, and specifically provide a draft assembly of L. ruthenicum and a chromosome-level assembly of L. barbarum, the wolfberry or Goji berry. From a phylogenetic tree the authors identify an ancient hexaploidization event, and report the evolution of gene families including fruit ripening, fruit coloration, polysaccharide synthesis and self-incompatibility within Solanaceae and the general biogeography of L. barbarum.

Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells. However, its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons remains unclear. The aim of this study was to investigate whether caveolin-1 regulates the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. We also examined whether the expression of caveolin-1 could be modulated by RNA interference technology to promote the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. The differentiation of human adipose mesenchymal stem cells into dopaminergic neurons was evaluated morphologically and by examining expression of the markers tyrosine hydroxylase, Lmx1a and Nurr1. The analyses revealed that during the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons, the expression of caveolin-1 is decreased. Notably, the downregulation of caveolin-1 promoted the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons, and it increased the expression of tyrosine hydroxylase, Lmx1a and Nurr1. Together, our findings suggest that caveolin-1 plays a negative regulatory role in the differentiation of dopaminergic-like neurons from stem cells, and it may therefore be a potential molecular target for strategies for regulating the differentiation of these cells. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University of China (approval No. PJ-KS-KY-2020-54) on March 7, 2017.

This article proposes a novel MPPT algorithm based on the firefly algorithm and elite ant system-trained Elman neural network (FA-EAS-ElmanNN). First, the position of fireflies is randomly initialized by the firefly algorithm (FA), meanwhile the firefly individuals with higher attractiveness degree value are selected as the optimal solution. Second, the extra pheromones are artificially released to boost the positive feedback effect and convergence rate of the elite ant system (EAS). Third, the weight and threshold of the Elman neural network (ElmanNN) are updated by the FA and EAS. Also, the trained ElamnNN is employed to acquire the maximum voltage of the photovoltaic (PV) array. At last, the PID controller and PWM technology are adapted to regulate the switch time of the boost converter. Furthermore, MATLAB/Simulink is adopted to acquire the datasets of irradiance, temperature, and maximum voltage and validate the reliability and superiority of the proposed algorithm under complex atmospheric conditions. The tracking characteristic, response speed, and efficiency of the proposed MPPT algorithm are contrasted with the particle swarm optimization (PSO), ant colony optimization (ACO), ACO-artificial neural network (ACO-ANN), and PSO-RBF neural network (PSO-RBNFNN) algorithm via simulation. The efficiency of the FA-EAS-ElmanNN algorithm is 99.73%, compared with the ACO-ANN, PSO-RBFNN, PSO, and ACO algorithm, which is increased by 0.49%, 0.58%, 1.2% %, and 1.5%, respectively. Additionally, the experimental setup is built to demonstrate the tracking characteristic of the proposed MPPT algorithm.

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

Mercury (Hg) is a kind of heavy metal pollutant widely existing in the aquatic environment, and it is also recognized to have a highly toxic effect on fish. In this study, silver carp (Hypophthalmichthys molitrix) larvae were exposed to 0 (control), 1, 5, and 10 μg/L Hg2+ for 2 weeks. Antioxidant ability, neurotoxicity, and thyroid hormones (THs) content were evaluated. In comparison with the control, the superoxide dismutase (SOD) activity and the glutathione (GSH) activity were lower in silver carp exposed to 10 μg/L Hg2+. The lowest catalase (CAT) activity was found in the 10 μg/L Hg2+, while malondialdehyde (MDA) content was not significantly different among all groups. Compared with the control, monoamine oxidase (MAO) activity and nitric oxide (NO) content were significantly higher in the 10 μg/L Hg2+, while acetylcholinesterase (AChE) activity significantly decreased. Compared with the control, triiodothyronine (T3) content was significantly higher in the 1 μg/L Hg2+ and significantly lower in the 10 μg/L Hg2+; the 1 μg/L and 5 μg/L Hg2+ groups had significantly higher thyroxine (T4) content than the other groups. In the 1 μg/L Hg2+, the integrated biomarker response (IBR) index value was the highest. In summary, exposure to Hg could decrease the antioxidant ability, cause changes in neurotoxic parameters, and induce disorders of the thyroid hormone system in silver carp larvae. The results of this study may contribute to the understanding of the adverse effects of chronic mercury poisoning on fish.

EAF stainless steel slag (EAF slag) is one kind of chromium-bearing metallurgical solid waste, which belongs to alkaline steel slag, and contains a large number of alkaline mineral phases. The carbonation activity of these minerals gives EAF slag the capability to effectively capture CO2. In this paper, EAF slag samples with different carbonation degrees were prepared by the slurry-phase accelerated carbonation route. The mineralogical identification analysis was used to qualitatively and semi-quantitatively determine the types and contents of the carbonatable mineral phases in the EAF slag. The sequential leaching test was used to study the chromium leachabilities in EAF slags with different carbonation degrees. The results showed that the main minerals with carbonation activity in EAF slag were Ca3Mg(SiO4)2 and Ca2SiO4, with mass percentages of 56.9% and 23%, respectively. During the carbonation process, Ca2SiO4 was the main reactant and calcite was the main product. As the degree of carbonation increased, the pH of the EAF slags’ leachate gradually decreased while the redox potential (Eh) gradually increased. At the same time, a large amount of Ca2+ in the EAF slag combined with CO2 to form slightly soluble calcium carbonate, which led to a significant decrease in the conductivity of the leachate. With the gradual increase in carbonation ratio, the leachability of chromium in the EAF slag first decreased and then increased, and reached its lowest value when the CO2 uptake ratio was 11.49%.

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

We studied gas-exchange, chlorophyll pigments, lipid peroxidation, antioxidant enzymes, and biomass partitioning responses in seedlings of four wolfberry species (Lycium chinense Mill. var. potaninii (Pojark.) A. M. Lu, Lycium chinense Mill., Lycium barbarum L., and Lycium yunnanense Kuang & A. M. Lu) under four water supply regimes. In all four species, drought affected seedlings in terms of chlorophyll content, net photosynthesis rate (Pn), transpiration rate (E), and lipid peroxidation. Drought also increased some antioxidant enzyme activities, such as peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX). Significant changes in dry biomass partitioning also occurred in response to water stress. In particular, dry biomass of leaves and fruits decreased significantly. L. chinense Mill. and L. barbarum L. possessed greater drought tolerance and exhibited superior antioxidant processing ability and other related physiological traits compared to the other two species. L. chinense Mill. was the most tolerant to all levels of drought. In contrast, L. yunnanense Kuang & A. M. Lu was more affected by water supply and had the lowest resistance to drought stress. These findings would provide some important information regarding genetic resources for future forest tree improvement in relation to drought tolerance.

The study mainly aims at the potential of Argon Oxygen Decarburization Slag (AODS) as a supplementary cementitious material and explores the mechanisms of stabilization/solidification (S/S) of chromium in cement-based composite pastes. The basic cementitious parameters, such as water requirement, setting time, soundness, hydration characteristics, and strength indexes of composite binders, were examined through standard methods. The results showed that the most beneficial mineral phase in AODS for cementitious behavior was beta dicalcium silicate (β-C2S). The utilization of a higher AODS dosage in composite binders increased the water requirement and the setting time, while it decreased the hydration heat and the strength indexes. Although the AODS possessed limited cementitious properties, it conformed the Grade II steel slag powder qualified for concrete and cement. Sequential leaching tests were conducted targeting the leachability of chromium in the pastes with different AODS dosage and curing time. Results showed that with the lower AODS dosage and the longer curing time, the S/S efficiency for chromium leaching from the composite paste was better. Utilization of AODS as a cement substitute not only can recycle this solid waste and decrease the emission of CO2 concerning cement production, but also helps to effectively reduce the chromium leaching risk.

For humans, nonvisual biological effects, which can be parameterized by the circadian action factor (CAF), are important for their health and work performance. In this paper, an approach by adjusting electrical currents of three-primary light-emitting diodes (RGB-LEDs) to tune the CAF and color coordinates to be close to those of the standard light with various correlated color temperature (CCT) (2700 K-6500 K) has been reported. This approach is based on deriving an empirical formula between the optical power and the electrical current. In order to meet the requirement of both high color rendering index (CRI) and better CAF, we theoretically perform further spectral optimization on RGB-LEDs and have found that peak wavelengths of 466, 547, and 615 nm for the blue, green, and red color component, respectively, turn out to be the best peak wavelength combination for obtaining both high CRI and high luminous efficacy of radiation of RGB-LEDs, while the CAF, CCT, and color coordinates of RGB-LEDs approach those of the standard light.

We consider a binary self-attractive Bose–Einstein condensate with Rashba spin–orbit coupling (SOC) in two-dimensional (2D) free space. The formation, stability, and dynamics of vector bright solitons are elucidated through numerical analysis and variational approximation. It is found that dynamically stabilized vector bright solitons can be formed in 2D free space with appropriate parameters and ramp schemes, and its motional trajectory and stability show nontrivial behavior and strong dependence on the direction of the force generated by the SOC. Finally, the case of the periodic modulation of SOC is discussed, and an experimental protocol is also given.

The newly proposed mimetic underpotential deposition (MUPD) technique was extended to modify Pd surfaces with Sb through immersing a Pd film electrode or dispersing Pd/C powder in a Sb(III)-containing solution blended with ascorbic acid (AA). The introduction of AA shifts down the open circuit potential of Pd substrate available to achieve suitable Sb modification. The electrocatalytic activity and long-term stability towards HCOOH electrooxidation of the Sb modified Pd surfaces (film electrode or powder catalyst) by MUPD is superior than that of unmodified Pd and Sb modified Pd surfaces by conventional UPD method. The enhancement of electrocatalytic performance is due to the third body effect and electronic effect, as well as bi-functional mechanism induced by Sb modification which result in increased resistance against CO poisoning.

Adenosine (Ado) is an important cardioprotective agent. Since endogenous Ado levels are affected by the enzyme Ado deaminase (ADA), polymorphisms within the ADA gene may exert some effect on chronic heart failure (CHF). This study applied a case-control investigation to 300 northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls in which nine single-nucleotide polymorphisms (SNPs) of ADA were genotyped and association analyses were performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. Overall, rs452159 polymorphism in ADA gene was significantly associated with susceptibility to CHF under the dominant model (p = 0.013, OR = 1.537, 95% CI = 1.10–2.16), after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the rs452159 according to the functional New York Heart Association class was found. Furthermore, the values of left ventricular ejection fraction, left-ventricle end-diastolic diameter or left-ventricle end-systolic diameter did not differ significantly among the different rs452159 genotype CHF patients. Although further studies with larger cohorts and other ethnicities are required to validate the conclusions, the findings of this study potentially provide novel insight into the pathogenesis of CHF.

Background: Although nonoperative management for perforated peptic ulcer (PPU) has been used for several decades, the indication is still unclear. A clinicoradiological score was sought to predict who can benefit from it. Methods: A clinicoradiological protocol for the assessment of patients presenting with PPU was used. A logistic regression model was applied to identify determinant variables and construct a clinical score that would identify patients who can be successfully treated with nonoperative management. Results: Of 241 consecutive patients with PPU, 107 successfully received nonoperative management, and 134 required surgery. In multivariable analysis, the following four variables correlated with surgery and were given one point each toward the clinical score: age ≥70 years, fluid collection detection by ultrasound, contrast extravasation detection by water-soluble contrast examination, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥8. Eighty-five percent of patients with a score of 1 or less were successfully treated with nonoperative management, whereas 23 of 29 patients with a score of 3 or more required surgery. The area under the receiver operating characteristic curve was 0.804 (95% confidence interval = 0.717–0.891). Conclusion: By combining clinical, radiological parameters, and APACHE II score, the clinical score allowed early identification of PPU patients who can benefit from nonoperative management.

Endometrial cancer (EC) is a complex disease involving multiple gene-gene and gene-environment interactions. TGF-β signaling plays pivotal roles in EC development. This study aimed to investigate whether the genetic polymorphisms of TGF-β signaling related genes TGFB1, TGFBR1, SNAI1 and TWIST1 contribute to EC susceptibility. Using the TaqMan Genotyping Assay, 19 tagging-SNPs of these four genes were genotyped in 516 EC cases and 707 controls among Chinese Han women. Logistic regression (LR) showed that the genetic variants of TGFB1 rs1800469, TGFBR1 rs6478974 and rs10733710, TWIST1 rs4721745 were associated with decreased EC risk, and these four loci showed a dose-dependent effect (Ptrend < 0.0001). Classification and regression tree (CART) demonstrated that women carrying both the genotypes of TGFBR1 rs6478974 TT and rs10512263 TC/CC had the highest risk of EC (aOR = 7.86, 95% CI = 3.42-18.07, P

In order to fully interpret and describe damage mechanics, the origin and development of fuzzy stochastic damage mechanics were introduced based on the analysis of the harmony of damage, probability, and fuzzy membership in the interval of [0,1]. In a complete normed linear space, it was proven that a generalized damage field can be simulated through β probability distribution. Three kinds of fuzzy behaviors of damage variables were formulated and explained through analysis of the generalized uncertainty of damage variables and the establishment of a fuzzy functional expression. Corresponding fuzzy mapping distributions, namely, the half-depressed distribution, swing distribution, and combined swing distribution, which can simulate varying fuzzy evolution in diverse stochastic damage situations, were set up. Furthermore, through demonstration of the generalized probabilistic characteristics of damage variables, the cumulative distribution function and probability density function of fuzzy stochastic damage variables, which show β probability distribution, were modified according to the expansion principle. The three-dimensional fuzzy stochastic damage mechanical behaviors of the Longtan rolled-concrete dam were examined with the self-developed fuzzy stochastic damage finite element program. The statistical correlation and non-normality of random field parameters were considered comprehensively in the fuzzy stochastic damage model described in this paper. The results show that an initial damage field based on the comprehensive statistical evaluation helps to avoid many difficulties in the establishment of experiments and numerical algorithms for damage mechanics analysis.

Littoral cell angioma (LCA) is a rare primary benign vascular neoplasm of the spleen. The case of a 52-year-old female with LCA is reported. The patient did not have any symptoms or a significant past medical history. Computed tomography (CT) and ultrasound (US) imaging studies showed multiple lesions in the spleen and gallbladder stones. The tumour was removed successfully by laparoscopic splenectomy and simultaneously cholecystectomy was conducted for gallbladder stones. The patient recovered uneventfully. The tumour lining cells were positive for CD31/CD68 markers, and negative for CD34. This is the first report of a LCA combined with gallbladder stones.

Owing to the complexity of geo-engineering seepage problems influenced by different random factors, three-dimensional simulation and analysis of the stochastic seepage field plays an important role in engineering applications. A three-dimensional anisotropic heterogeneous steady random seepage model was developed on the basis of the finite element method. A statistical analysis of the distribution characteristics of soil parameters sampled from the main embankment of the Yangtze River in the Southern Jingzhou zone of China was conducted. The Kolomogorov-Smirnov test verified the statistical hypothesis that the permeability coefficient tensor has a Gaussian distribution. With the help of numerical analysis of the stochastic seepage field using the developed model, various statistical and random characteristics of the stochastic seepage field of the main embankment of the Yangtze River in the Southern Jingzhou zone of China were investigated. The model was also examined with statistical testing. Through the introduction of random variation of the upstream and downstream water levels into the model, the effects of the boundary randomness due to variation of the downstream and upstream water levels on the variation of simulated results presented with a vector series of the random seepage field were analyzed. Furthermore, the combined influence of the variation of the soil permeability coefficient and such seepage resistance measures as the cut-off wall and relief ditch on the hydraulic head distribution was analyzed and compared with the results obtained by determinate analysis. Meanwhile, sensitivities of the hydraulic gradient and downstream exit height to the variation of boundary water level were studied. The validity of the simulated results was verified by stochastic testing and measured data. The developed model provides more detail and a full stochastic algorithm to characterize and analyze three-dimensional stochastic seepage field problems.

This study aims to investigate whether the germline variants in CDH1 and CTNNB1 would affect breast cancer susceptibility and patients' prognosis among Chinese Han women using a haplotype-based association analysis. We genotyped 12 haplotype-tagging single nucleotide polymorphisms (htSNPs) in CDH1 and CTNNB1 among 1,160 BC cases and 1,336 age-matched cancer-free controls using the TaqMan® Genotyping Assay. For association analyses of germline variants with breast cancer susceptibility, the results showed that rs7200690, rs7198799, rs17715799, rs13689 and diplotype CGC/TGC (rs7200690 + rs12185157 + rs7198799) in CDH1 as well as rs2293303 in CTNNB1 were associated with increased breast cancer risk. In addition, the Generalized Multifactor Dimensionality Reduction (GMDR) and logistic regression analysis predicted an interaction on breast cancer risk between rs17715799 and rs13689 as well as rs13689 and menarche-FFTP (First Full-Term Pregnancy) interval. For survival analyses, the results demonstrated that the minor allele homozygotes of rs13689 and haplotype TGC in CDH1 were linked with unfavorable event-free survival of breast cancer, whereas, rs4783689 of CDH1 showed the opposite effect under dominant model. Notably, the stratified analysis revealed that rs7186053 was associated with favorable event-free survival among patients with estrogen receptor (ER)-positive, progesterone receptor (PR)-positive or lymph node metastasis negative patients. Moreover, rs7200690 and rs7198799 in CDH1 as well as rs4533622 in CTNNB1 were associated with worse event-free survival among patients with clinical stage 0-I tumors. This study indicated that the genetic polymorphisms of CDH1 and CTNNB1 were associated with breast cancer susceptibility and patients' prognosis.

Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.

Influenza virus, which spreads around the world in seasonal epidemics and leads to large numbers of deaths every year, has several ribonucleoproteins in the central core of the viral particle. These viral ribonucleoproteins can specifically bind the conserved 3' and 5' caps of the viral RNAs with responsibility for replication and transcription of the viral RNA in the nucleus of infected cells. A fundamental question of most importance is that how the cap-binding proteins in the influenza virus discriminates between capped RNAs and non-capped ones. To get an answer, we performed molecular dynamics simulations and free energy calculations on the influenza A virus PB2 subunit, an important component of the RNP complexes, with a cap analog m7GTP. Our calculations showed that some key residues in the active site, such as Arg355, His357, Glu361 as well as Gln406, could offer significant hydrogen bonding and hydrophobic interactions with the guanine ring of the cap analog m7GTP to form an aromatic sandwich mechanism for the cap recognition and positioning in the active site. Subsequently, we applied this idea to a virtual screening procedure and identified 5 potential candidates that might be inhibitors against the PB2 subunit. Interestingly, 2 candidates Cpd1 and Cpd2 have been already reported to have inhibitory activities to the influenza virus cap-binding proteins. Further calculation also showed that they had comparatively higher binding affinities to the PB2 subunit than that of m7GTP. We believed that our findings could give an atomic insight into the deeper understanding of the cap recognition and binding mechanism, providing useful information for searching or designing novel drugs against influenza viruses.

The title compound, C18H22O6, was obtained by the domino oxa–Michael–aldol (DOMA) reaction and has the cyclohexanone ring in a chair conformation with intra-annular torsion angles in the range 49.9 (2)–58.9 (2)°. The two ethoxycarbonyl substituents on the cyclohexanone ring adopt a syn configurations. In the crystal, the molecules self-assemble through duplex intermolecular hydroxy–carbonyl O—H...O hydrogen bonds, giving centrosymmetric cyclic dimers [graph set R22(12)] which inter-associate through weak C—H...O hydrogen-bonding interactions.

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Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis. [ABSTRACT FROM AUTHOR]