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Abstract Background Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions before 20 weeks with the same spouse [1]. However, approximately 50% of RSA cases of unknown cause are classified as unexplained recurrent spontaneous abortion (URSA). Potential factors include decreased trophoblast cell migration and invasion, leading to impaired placental implantation and maintenance of the normal maternal-fetal interface. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the potential role and mechanism of KLF4 in regulating URSA by influencing the invasion and migration ability of trophoblast cells. Methods We firstly identified 817 differentially expressed genes by performing a difference analysis of the dataset GSE121950 [2] related to recurrent abortion, and intersected the top 10 genes obtained respectively by the three algorithms: DMNC, MNC, and EPC using Venn Diagram.To detect the expression levels of core genes, villi samples were obtained from normal pregnant women and patients with URSA. RT-qPCR analysis revealed a significant difference in KLF4 mRNA expression and KLF4 was then analyzed. Trophoblast cell lines HTR8 and JEG3 were used to investigate the effect of KLF4 on trophoblastic function. Wound healing and transwell assays was performed to detect the invasion and migration of trophoblast cells. The expression of epithelial-mesenchymal transition(EMT) molecules were detected by RT-qPCR and western blot. Promoter detection and epigenetic modification were detected by chromatin immunoprecipitation (ChIP) assay. Molecular nuclear localization was detected by immunofluorescence and subcellular fractionation. Miscarried mice model was used to study the effects of KLF4 on URSA induced by reduced trophoblast invasion and migration. Results KLF4 is highly expressed in the villi of patients with URSA. KLF4 inhibits the expression level of H3R2ME2a in trophoblast cells by regulating the transcriptional level and nuclear translocation of PRMT6, thereby inhibiting the possible regulatory mechanism of trophoblastic invasion and providing a potential treatment strategy for URSA in vivo. Conclusions The KLF4/PRMT6/H3R2ME2a axis regulates mechanisms associated with unexplained recurrent spontaneous abortion by regulating trophoblast function.

Abstract During geomagnetic storms, geomagnetically induced currents (GICs) occur in the power grid. GIC is a quasi‐direct current, which is represented by using a fixed DC current, the authors propose an approach that combines field‐circuit‐coupled and weakly coupled magneto‐mechanical models to investigate the magnetostriction characteristics of single‐phase, four‐column autotransformer cores excited by GICs. A non‐linear magnetostrictive constitutive model that considers the impact of stress and magnetisation intensity on ferromagnetic materials is introduced. The model reveals that the strain in the core initially increases as the magnetisation intensity increases; however, when the core begins to saturate, the magnetostrictive strain weakens as the magnetisation intensity increases. Moreover, the results of multiphysics finite‐element modelling are experimentally verified using a direct current bias platform. The results show that when excited by GICs, there is an enhancement in the vibration of the iron core, and the harmonic content of the vibration acceleration increases considerably, with the odd harmonics most significantly increasing in amplitude. The conclusion drawn is that GICs can exacerbate transformer vibration and significantly increase the content of harmonics, especially odd harmonics.

PIM1, the proviral integration site for Moloney murine leukemia virus, is a member of the serine/threonine protein kinase family. It is involved in many biological events, such as cell survival, cell cycle progression, cell proliferation, and cell migration, and has been widely studied in malignant diseases. However, recent studies have shown that PIM1 plays a prominent role in immunoinflammatory diseases, including autoimmune uveitis, inflammatory bowel disease, asthma, and rheumatoid arthritis. PIM1 can function in inflammatory signal transduction by phosphorylating multiple inflammatory protein substrates and mediating macrophage activation and T lymphocyte cell specification, thus participating in the development of multiple immunoinflammatory diseases. Moreover, the inhibition of PIM1 has been demonstrated to ameliorate certain immunoinflammatory disorders. Based on these studies, we suggest PIM1 as a potential therapeutic target for immunoinflammatory diseases and a valid candidate for future research. Herein, for the first time, we provide a detailed review that focuses on the roles of PIM1 in the pathogenesis of immunoinflammatory diseases.

Given the abundance and intricate nature of the chemical components found in natural food ingredients, functional food research has long grappled with two significant technical challenges: rapid and precise screening of active substances and targeted preparation. To enhance the efficiency of fungal food preparation, novel methodologies for screening and the production of xanthine oxidase inhibitors from G. lucidum have been developed. The xanthine oxidase inhibitors were rapidly screened using AUF-LC-MS. Molecular docking and molecular dynamics simulation were used to verify the anti-gout activity of active compounds. Subsequently, with activity screening as the guide, HSCCC and SPLC were employed to separate the active ingredients. Simultaneously, the mechanism of action of xanthine oxidase inhibitors was analyzed by enzymatic reaction kinetics. Finally, the anti-gout activity of chemical components in G. lucidum was verified by network pharmacology, and its mechanism of action was discussed. Four potential xanthine oxidase inhibitors, namely ganoderic acid C2, B, A, and D2, were screened from G. lucidum. Their docking binding energies with xanthine oxidase were −6.29, −6.65, −4.29, and −5.96 kcal/mol, respectively. The purity of the four triterpenoid active ingredients isolated from G. lucidum was more than 90 %. These triterpenoid active ingredients showed a reversible inhibitory effect on xanthine oxidase. Network pharmacological studies revealed 71 common targets of active ingredients and gout, obtained by screening and intersecting the two targets, and identified the main metabolic pathways. The results indicate that G. lucidum extract can be employed for the prevention and treatment of gout disease. We enhance the efficiency and purity of active compounds preparation by incorporating enzyme inhibition assays and computerized virtual screening with compound chromatography. With this approach, we seamlessly incorporate fast discovery, screening, and focused preparation of active ingredients, as well as delving into the mechanisms of action of active monomers and proteases, and the molecular-level interactions between active ingredients and proteases. This study providing more opportunities to discover and develop new potential therapeutics from health food resources.

IntroductionThis study aimed to investigate the regulatory effects of mulberry leaf flavonoids and carnosic acid complex (MCC) on the growth performance, intestinal morphology, antioxidant, and p38 MAPK/Nrf2 pathway in broilers.MethodsA total of 256 healthy 8-day-old female yellow-feathered broilers were randomly divided into 4 equal groups: a control group (CON) fed a basal diet, an antibiotic group (CTC) supplemented with 50 mg/kg chlortetracycline, and two experimental groups (MCC75, MCC150) fed basal diets with 75 mg/kg and 150 mg/kg of MCC, respectively. The experiment lasted for 56 days, with days 1–28 designated as the initial phase and days 29–56 as the growth phase.ResultsThe results on the growth performance showed that diets supplemented with MCC and CTC decreased the feed-to-gain ratio (F/G), diarrhea rate, and death rate, while significantly increasing the average daily weight gain (ADG) (p

There are many types of sources and loads in the electricity-heating coupling integrated energy system, and there are correlation characteristics between different energy sources, between loads, and between energy sources and loads, and the uncertainty of source and load is becoming more and more significant. In this regard, a calculation method of electricity-heating coupling probabilistic multi-energy flow considering the correlation and uncertainty of input variables is proposed in this paper. Firstly, the uncertainty probability models of wind power generation, photovoltaic generation, solar heat pump, heat load, and electricity load are established respectively; Secondly, the triangular fuzzy number is proposed to describe the correlation between variables, and the fuzzy correlation model of random variables of source and load is established by means of Gauss–Hermite integral and Nataf inverse transformation; Finally, the output state variables are fitted using the cumulant method and Cornish–Fisher series expansion to obtain the probability distribution of the output variables. The feasibility and effectiveness of the proposed method is verified by using an electricity-heating coupling integrated energy system. At the same time, the influence of fuzzy correlation intervals and coefficient changes on the probability distribution of output variables, and the influence of heat load fluctuations on the nodal voltage probability distribution of the power supply system are analyzed.

With climate change, extreme weather is occurring frequently, which can cause serious damage to energy supply systems. It is of great significance to study the performance of power transmission system under extreme weather for prevention and reinforcement before and after disasters. This paper proposes a time-domain simulation model for quantifying power system resilience under extreme typhoon scenario. Firstly, the power system resilience assessment method based on global maximum flow (GMF) is presented, which is applied to map the overall system operation performance via creating a network indicator while considering component fragility, system topology, and power flow. A specific resilience expression (RES) is proposed to describe percentage improvement of each component in the resilience metrics by considering the overall system performance. Secondly, power system vulnerability model and time-domain simulation methodology are established. The proposed method is demonstrated by four case studies using the IEEE-30 node test system under specific typhoon scenarios. From the GMF based RES index, the component repair strategy is formulated accordingly. The proposed restoration strategy, compared with the traditional expert strategy can effectively measure the resilience contribution of each component to the whole power system, and minimizes the power system performance losses due to extreme typhoon. The proposed approach quantitatively evaluates real-time system resilience to extreme typhoons, and it can also identify the system critical areas and assess the benefits of different resilience enhancement strategies. The resilience assessment framework can also be applied to other extreme scenarios and contribute to planning and construction of strong smart grid in the future.

The growing expansion of the economy and population has resulted in an increased inclination towards the utilization of groundwater resources. Conducting a geophysical survey is a widely employed method for subsurface mapping and the detection of groundwater. A geophysical study was conducted in Nanshan township, Huarong County, located in the Hunan province of the South-Central region of China. The investigation involved the utilization of a 2D electrical resistivity imaging technique employing forward and inverse pole–dipole electrode arrays. A total of six survey lines were established, each with an electrode distance from the nearest measuring point exceeding 800 m. The maximum current electrode separation was utilized in this setup. The spacing between the electrical resistivity sounding points was established at regular intervals. The findings from the exploration indicate the existence of multiple faults within the surveyed region. The study additionally identified two regions of structural failure, which occurred due to the convergence of faults oriented in different directions. This convergence led to the fracturing of rocks, an increase in water content, and a decrease in resistivity. The findings from the exploration were utilized in the formulation of five verification target boreholes. The results of this study offer significant insights that can inform future investigations into groundwater exploration endeavors within the region.

The Washan iron deposits in Ningwu district contain different magma-related genetic natures, including magmatic, magmatic–hydrothermal and hydrothermal types, and their ore-forming processes remain a subject of debate. To elucidate the ore-forming processes of iron ores from Washan, we present textural, major element analytical, and thermal data of magnetites from various ore bodies in Washan, probing the crystallization conditions and subsequent formation sequence of magnetites. SEM analysis with back-scattered electron (BSE) imaging reveals diverse magnetite textures, including mineral inclusions, exsolution lamellae, and recrystallization features, reflecting the transitional environment from magmatic to hydrothermal. Based on Ti, V, and Cr compositions of magnetite from different ore bodies, two distinct evolution trends of genetic processes are identified, including evolution paths from porphyry-type to IOA- and IOCG-type magnetite. High-resolution WDS mapping highlights the intensifying alterations during this process. Calculated magnetite crystallization temperatures among different types of magnetite range from 597 °C to 378 °C, suggesting a cooling trend from porphyry-type magnetite (~558 °C) to IOA-type magnetite (~515–439 °C) and IOCG-type magnetite (~378 °C). These results underscore the significant role of magma-derived hydrosaline liquids and vapors in the formation of iron ores from Washan, where variations in the salinity of ore-forming fluids lead to different evolutionary paths for subsequent generations of magnetite. The metallogenic model of the Washan iron deposit suggests that highly saline, iron-rich fluids connect the varying geneses of magnetite, transitioning from deeply formed porphyry-type magnetite to IOA- or IOCG-type magnetite generated in the subaerial zone.

Single-molecule localization microscopy circumvents the diffraction limit of traditional fluorescence microscopy by detecting the photoemission signals of individual fluorescent molecules. The accurate recognitions of fluorescence molecules/events are critical to single-molecule/super-resolution imaging experiments, which determine the precision of molecular localizations and the quality of the image reconstruction. Herein, we presented a single-molecule detection method which relied on the temporal pixel intensity fluctuation. The method was capable of quickly determining the approximate localizations of fluorescence events with high sensitivity. We evaluated the performance of the method under a series of signal-to-noise ratios (SNR) and discussed the criterion of setting the temporal fluctuation threshold to achieve the optimized spots recognition results.

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The efficacy of the top hit, Erlotinib, extended to human cells, where it blocked Wnt/β-catenin signaling downstream of the destruction complex. Notably, Erlotinib treatment reduced self-renewal in human T-cell Acute Lymphoblastic Leukemia cells, which rely on active β-catenin signaling for maintenance of leukemia-initiating cells. Erlotinib also reduced leukemia-initiating cell frequency and delayed disease formation in zebrafish models. This study underscores zebrafish’s translational potential in drug discovery and repurposing and highlights a new use for Erlotinib as a Wnt inhibitor for cancers driven by aberrant Wnt/β-catenin signaling.

Grain size, characterized by a combination of grain length, width, and thickness, is one of the major determinants of yield in rice. The present study identified TATA-box binding protein-associated factor 2 (TAF2) as an essential component regulating transcription and determining grain size in rice. Map-based cloning showed that a G/T substitution in TAF2 resulted in a naturally occurring mutant called reduced grain size and plant height 1 (rgh1). The mutants, with weak edited rgh1 alleles, exhibited a small grain phenotype with reduced grain length and width, while the severe knockout mutant (rgh1-2s) was dwarf and completely sterile. Allelic test performed between rgh1 and several edited alleles confirmed that the mutation in TAF2 caused the rgh1 phenotype. GUS staining showed that TAF2 was mainly expressed in the vascular bundles of roots, stems, leaves, and grains. The cytological analysis revealed that reduced cell division in the glumes resulted in the small grain phenotype of rgh1. Further RNA-sequencing detected altered expression of genes involved in the basic biological processes in rgh1 mutant. These findings provide novel insights into the TAF2-mediated genetic mechanism regulating grain size in rice.

In recognizing the pervasive nonstationarity of hydrometeorological variables, a paradigm shift towards alternative analytical methodologies is imperative for refining hydroclimatic data modeling and prediction. We introduce a novel approach leveraging nonstationary Graphical Modeling and Bayesian Networks (NGM-BNs) tailored for hydrometeorological applications. Demonstrated through monthly streamflow forecasting in the Kashgar River Basin of China, our method illuminates the temporal evolution of network relationships, underscoring the dynamism inherent in both input variables and modeling parameters. The key to our approach is identifying the most suitable time horizon (MST) for model updates, which is intricately problem-specific and crucial for peak performance. This methodology not only unveils changing predictor significance across varying flow conditions but also elucidates the fluctuating temporal links between variables, especially under the lens of climate change, for instance, the growing impact of snowmelt on the Kashgar Basin’s streamflow. Compared to stationary counterparts, our nonstationary Bayesian framework excels in capturing extreme events by adeptly accommodating temporal shifts, outperforming traditional models including both stationary and nonstationary variants of Support Vector Regression (SVR) and Adaptive Neuro-Fuzzy Inference Systems (ANFIS).

IntroductionBlack/purple rice is a pigmented rice variety that contains high levels of anthocyanins, flavonoids, and other valuable bioactive compounds. Owing to its robust anti-inflammatory and antioxidant properties, black/purple rice exerts a beneficial effect on human health. Extrusion puffing technology has emerged as a promising means of improving rice flavor with lesser effect on nutrient content. In this study, metabolomics approach was used to conduct comprehensive metabolomics analyses aimed at examining the impact of extrusion puffing on black/purple rice nutritional value and flavor.MethodsFirstly, the basic nutrient composition contents and extrudate characteristics of black/purple rice and Extrusion puffed black/purple rice were conducted. Then metabolomics profiling analyses of black/purple rice samples were performed to explore the impact of the extrusion puffing process on nutrient content and bioactive properties, in which we quantitatively determined the flavonoids and evaluated relative contents of volatile compounds.ResultsThese analyses revealed that following extrusion puffing, black/purple rice exhibited significant improvements in the content of nutrients including flavonoids, minerals, and proteins together. Extrusion puffing additionally increased the diversity of volatile compounds within black/purple rice.DiscussionThese results suggest that extrusion puffing represents an effective means of substantially improving the functional and nutritional properties of black/purple rice, offering beneficial effects on consumer health. Overall, these data provide novel insights into the quality of extrusion puffed black/purple rice that will guide future efforts to establish how extrusion puffing can alter the nutrient content in a range of foods, thereby supporting the further development of a range of healthy food products.

Abstract Temperature has an important influence on plant growth and development. In protected agriculture production, accurate prediction of temperature environment is of great significance. However, due to the time series, nonlinear and multi coupling characteristics of temperature, it is difficult to achieve accurate prediction. We proposed a method for building a solar greenhouse temperature prediction model based on a timeseries analysis, that considers the time series characteristics and dynamic temperature changes in the greenhouse system. The method would predict the temperature of greenhouse, and provide reference for the temperature change law in protected agriculture. A parameter analysis was performed on the nonlinear autoregressive exogenous (NARX) neural network, and a solar greenhouse temperature time series prediction model was established using the NARX regression neural network. The results showed that the proposed model depicted a maximum absolute error of 0.67 °C, and model correlation coefficient of 0.9996. Compared with the wavelet and BP neural networks, the NARX regression neural network accurately predicted and significantly outperformed in the solar greenhouse temperature prediction model. Moreover, the prediction model can accurately predict temperature trends within the solar greenhouse and is pivotal to obtaining precise control of solar greenhouse temperature.

Abstract Background Acute lymphoblastic leukemia is an aggressive neoplasm and seriously threatens human health. A14 is one kind of semisynthetic aurone that exhibits the capability to inhibit prostate cancer, but little is known about the role of A14 on T-cell acute lymphoblastic leukemia. Methods Firstly, the effects of A14 on the ability of leukemia cells to proliferate were measured by Vi-cell counter. Then, we detected the cell cycle and apoptosis by flow cytometry and characterized the related protein expression using immunoblotting. In addition, we constructed stable luciferase expressing cell lines for use in a cell derived xenograft mouse model to measure the effect of A14 on T-cell acute lymphoblastic leukemia. Results Results exhibited that A14 markedly suppressed cell proliferation and induced G2/M phase arrest along with cell cycles regulating proteins changes. A14 led to apoptosis in leukemia cells, at least partly, through the cytochrome c signaling pathway. Experiments in cell derived xenograft mouse model also showed that A14 markedly ameliorated the survival rate. Conclusions The present study revealed that semisynthetic aurones A14 can effectively protect against T-cell acute lymphoblastic leukemia progression both in vitro and in vivo, indicating the capability of A14 as a promising drug for the treatment of T-cell acute lymphoblastic leukemia.

Abstract Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.

This paper aimed to investigate the extraction process of total flavonoids and triterpenes in Inonotus obliquus by ultrasound-assisted enzymatic extraction. The UV spectrophotometric method was used as the detection method, the extraction rate of total triterpenes and flavonoids was used as the evaluation index, the effects of enzyme addition, enzymatic digestion time, liquid to material ratio and ethanol concentration on the extraction rate were investigated, and the best extraction process was obtained by NSGA-II genetic algorithm combined with response surface analysis. Finally, the main chemical components in Inonotus obliquus were analyzed and identified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The optimal extraction process for simultaneous extraction of total triterpenes and flavonoids from Inonotus obliquus was obtained by the Pareto front surface B region scheme, and the optimal extraction conditions were determined as enzyme addition of 1.9%, enzymatic digestion time of 45 min, liquid to material ratio of 20 mL/g, and ethanol concentration of 64%. The average extraction rates of total triterpenes and flavonoids were 2.670%±0.05% and 5.356%±0.09%, and the relative errors were 0.75% and 0.70% with the predicted average extraction rates. It was identified that Inonotus obliquus contained four active ingredients: Betulin, lanosterol, osmundacetone and quercetin. The above proved that the test indexes of NSGA-II genetic algorithm combined with response surface optimization of Inonotus obliquus fungus extraction process fitted well with the predicted results.

Tunnel boring machine (TBM) cutter ring material is a type of C–Cr–Mo–V alloy steel which possesses high hardness and wear resistance. To systematically study the effect of tempering temperature on the microstructure, mechanical properties and abrasive wear behavior of TBM cutter ring, a new C–Cr–Mo–V alloy steel (DB3) was subjected to tempering treatment and abrasive wear test. The results indicate that the tempering temperature controlled the hardness and toughness by adjusting the amount of precipitates and austenite transformation. Outstanding mechanical properties were obtained upon tempering at 520 °C. The wear resistance of DB3 steel was mainly controlled by hardness under non-impact abrasive wear condition. However, under the condition of impact abrasive wear, the wear resistance of DB3 steel was affected by hardness and toughness, and only in a certain range of toughness, the wear resistance increased with the increase of hardness. The experimental results can provide some reference for the heat treatment process of DB3 steel used in TBM cutter ring.

C–Cr–Mo–V martensitic steel possesses high hardness, toughness and wear resistance, which benefits from the coordination of tempered martensite and alloy carbide in its microstructure. The size, content and distribution of alloy carbide have a great influence on the properties of steel. In this paper, the carbide characteristics and matrix microstructure of experimental steel were adjusted by controlling forging ratio. The results show that with the increase of forging ratio, the primary carbides distribute more homogeneously in the matrix and the amount of secondary carbides increases gradually, which enhances the pinning effect on grain boundary and refines the prior austenite grain. The hardness and impact toughness increase simultaneously with the increase of forging ratio, which benefits from the refinement of carbide and prior austenite grain. The increase of forging ratio not only promotes the refinement and dissolution of primary carbides, but also contributes the precipitation of secondary carbides. Therefore, the influence of forging ratio on the wear resistance is more complex. When the forging ratio reachs 6 or12, the wear resistance of experimental steel is enhanced which benefits from the higher content and finer size of primary carbides under small forging ratio, and the refinement of martensite matrix, uniform distribution of primary carbides and precipitation of secondary carbides under large forging ratio.

Stroke is a serious disease caused by the rupture or blockage of the cerebrovascular system. Its pathogenesis is complex and involves multiple mechanisms. Iristectorin B is a natural isoflavone that has certain anti stroke effects. In this study, an in vitro stroke injury model of glyoxylate deprivation was established using PC12 cells, which was used to evaluate the anti-stroke activity of Iristectorin B in ejecta stem. The results showed that Iristectorin B, a natural isoflavone derived from Dried Shoot, significantly reduced the damage to PC12 cells caused by oxygen glucose deprivation/reoxygenation, decreased apoptosis, enhanced cell survival and reduced Ca2+, LDH and ROS levels. The results showed that Iristectorin B had a significant protective effect on Na2S2O4-injured PC12 cells, and the mechanism may be related to the protective effect of neurons in the brain. After protein extraction and various analyses were performed, a series of cutting-edge technologies were organically combined to study the quantitative proteome of each group. Differential proteins were then analyzed. According to the protein screening principle, ferroptosis-related proteins were most closely associated with stroke. The differential proteins associated with ferroptosis screened were SLC3A2, TFR1 and HMOX1, with HMOX1 being the most significantly elevated and reduced via dosing. Iristectorin B may act as a protective agent against stroke by regulating ferroptosis, and SLC3A2, TFR1 and HMOX1 may serve as potential diagnostic biomarkers for stroke, providing additional evidence to support the importance of ferroptosis in stroke.

A strategy based on representative volume element (RVE) was proposed to investigate the mechanical behavior of cold-drawn pearlitic steels at multiscale. Firstly, a finite element model based on macroscale was used to simulate the cold drawing. The partial mesh of the model was refined to obtain a RVE-scale element, and the elastic-plastic strain of this element were extracted and mapped to the RVE model. For further research, a high-resolution RVE model based on the crystal plasticity finite element method (CPFEM) was established to investigate the mechanical behavior of the pearlite. In addition, a new method of hierarchical partition was used for geometric modeling. Crucially, the simulated pole figures were in high agreement with the experimental results, both prominently showing an α-fiber texture. The final results indicated that the plasticity and strength of the pearlitic steels were determined by the coordinated deformation between pearlite nodules and the interaction between ferrite and cementite.

The effects of Sn content on the age-hardening behavior and peak aging precipitates of Al–Mg–Si alloys at 250 °C were investigated by hardness testing, scanning electron microscopy, transmission electron microscopy and high-resolution transmission electron microscopy. The results indicated that the peak hardness of the experimental alloys initially increased and then decreased with Sn content increasing from 0 to 0.15 wt.%, and it reached a maximum value of 108 HV in the alloy containing 0.1 wt.% Sn. All the Sn-added alloys exhibited higher peak hardness than the Sn-free alloy. Microstructure observations revealed that the enhanced peak hardness of the Sn-added alloys derived from the refinement of precipitates and their increase in number density. The underlying mechanisms of varying Sn addition contents on the precipitate microstructure were discussed.

ObjectiveTo screen and analyze the genetic mutations in the PPP1CB gene in a patient with Noonan syndrome with loose anagen hair-2 (NSLH2) in Yunnan Province, China and explore the possible molecular pathogenesis.MethodsAfter obtaining informed consent, we collected the patient's medical history and carried out physical and laboratory examinations for the NSLH2 proband and the family members. Genomic DNA was extracted from the peripheral blood of all individuals. The coding regions including all pathogenic exons, parts of introns, and promoters of genes were sequenced by next-generation sequencing. Pathogenic mutations, which were detected in the probands and their parents, were verified by Sanger sequencing.ResultsThe clinical manifestations of NSLH2 included prominent forehead, yellowish hair, slightly wide eye distance, sparse eyebrows, bilateral auricle deformity, reduced muscle tension, and cardiac and visual abnormalities. The proband carried a c.371A>G mutation in exon 3 of PPP1CB, which is a missense mutation. This was a de novo mutation as the parents of the proband showed no mutation at this site.ConclusionIn this study, we identified a novel mutation of PPP1CB, which enriched the mutation spectrum of the PPP1CB gene and provided a basis for the diagnosis of NSLH2.

In order to study the regulation of Fenugreek seed extract (FSE) on the immunity of broilers, and explore the appropriate amount of FSE in broilers' production, 1-day-old yellow feather broilers with a total of 420 birds were randomly allocated into seven treatments. Each treatment had six replicates, with 10 birds per replicate. The two control groups were the basic fodder group fed with basal diet and the bacitracin zinc group added 30 mg/kg bacitracin zinc to the basal diet. Experimental groups included five levels of FSE (50, 100, 200, 400, and 800 mg/kg FSE to the basal diet, respectively). The pre-test period was 7 days and the formal test lasted for 56 days. The results showed that the average daily gain (ADG) of 50 and 800 mg/kg FSE groups was significantly increased (P < 0.01), and the feed to gain ratio (F/G) of FSE groups was significantly decreased (P < 0.01) compared with the basic fodder and the bacitracin zinc groups. Compared with the basic fodder group, the serum total cholesterol (TC) content in the FSE groups was significantly decreased (P < 0.05), the serum low density lipoprotein cholesterol (LDL-C) content of 50, 100, and 800 mg/kg FSE groups was significantly lower than that of the basic fodder group (P < 0.05). Compared with the basic fodder and bacitracin zinc groups, the serum immunoglobulins (IgG, IgM, IgA) content of 100 and 200 mg/kg FSE groups were significantly increased (P < 0.05). Compared with the bacitracin zinc group, the serum interleukins (IL-1, IL-10) content of 400 mg/kg FSE group were significantly increased (P ≤ 0.05), and the serum interferon-γ (IFN-γ) content of 100 and 200 mg/kg FSE groups was significantly increased (P < 0.05). Compared with the basic fodder group, the lower doses (0–400 mg/kg) of FSE had no significant effect on the mRNA expression of toll-like receptors 4/ myeloid differentiation factor 88/ nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathways (P > 0.05). The 800 mg/kg FSE treatment group significantly increased the expression levels of nuclear factor-κB (NF-κB) mRNA in the spleen of broilers (P < 0.05). The zinc bacitracin group significantly increased the expression levels of myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) mRNA (P ≤ 0.05). The results showed that FSE could promote the secretion of immunoglobulins, regulate the body's cytokines, and have a positive effect on immunity in broilers. Furthermore, the recommended supplement of FSE is 100 mg/kg in the broiler diet.

The microstructure of solution-annealed and aged tensile properties and the stress rupture properties of 15Cr–15Ni titanium-modified austenitic stainless steel with different phosphorus contents were investigated using OM, SEM and TEM. The results showed that two phosphide morphologies were observed after long-term isothermal aging at 850 °C for 1000 h. One was the needle-like M2P distributed within the grain. The other was the blocky M3P distributed at the grain boundaries and twins. The tensile properties of the alloy were unaffected by the phosphorus content, but the stress rupture properties were significantly impacted. With the increase in the phosphorus content from 70 ppm to 250 ppm, the stress rupture life increased from 148 to 269.7 h. Since the strengthening effect of phosphides within the grain or at the grain boundary has been shown to improve the stress rupture properties of alloys, many nanosized granular precipitates, such as the sigma phase, carbides and phosphides, have been observed at the grain boundary, capable of alleviating the stress concentration and limit the crack propagation between two phases, improving the strength of the grain boundary. Intragranular needle-like phosphides can hinder dislocation movements effectively, which improves the intragranular strength of alloys.

The deregulation in the Wnt/β-catenin signaling pathway is associated with many human cancers, particularly colorectal cancer (CRC) and, therefore, represents a promising target for drug development. We have screened over 300 semisynthetic and natural compounds using a Wnt reporter assay and identified a family of novel chalcone derivatives (CXs) that inhibited Wnt signaling and CRC cell proliferation. Among them, we selected CX258 for further in vitro and in vivo study to investigate the molecular mechanisms. We found that CX258 significantly inhibited β-catenin expression and nuclear translocation, inducing cell cycle arrest at the G2/M phase in CRC cells. Additionally, CX258 reduced the expression of DNA Topoisomerase II alpha (TOP2A) in CRC cells. Moreover, knocking down TOP2A by siRNAs inhibited the Wnt/β-catenin signaling pathway, a finding suggesting that CX258 inhibited Wnt/β-catenin signaling and CRC cell proliferation at least partially by modulating TOP2A. Further studies showed that CDK1 that interacts with TOP2A was significantly reduced after TOP2A knockdown. We demonstrated that CX258 significantly inhibited DLD-1 CRC cell xenografts in SCID mice. In summary, we identified CX258 as a promising candidate for colorectal cancer treatment by targeting the TOP2A/Wnt/β-catenin signaling pathway.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can lead to severe social behavioral difficulties, which mainly manifests as social communication and interaction disorders; narrow interests; and repetitive, stereotyped behaviors. In recent years, the prevalence of ASD has increased annually, and it has evolved from a rare disease to one with a high incidence among childhood developmental disorders. The pathogenesis of ASD is considered to be the interaction of genetic and environmental factors. There is increasing evidence that vitamin D deficiency in pregnancy and early childhood can lead to the occurrence of ASD. Studies have demonstrated that vitamin D intervention can significantly improve the symptoms of ASD, but the underlying mechanism is still unclear. Therefore, exploring the neuroprotective mechanism of vitamin D against ASD is a huge challenge currently being worked on by current basic and clinical researchers, a task which is of great significance for the clinical promotion and optimization of vitamin D in the treatment of ASD. To further clarify the relationship between vitamin D and ASD, this review summarizes the correlation between vitamin D level and ASD, the effects of vitamin D supplementation on ASD, the possible mechanism of vitamin D involved in ASD, and insights from ASD animal models.

Resveratrol (RSV) is a natural polyphenolic compound with potent antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects of RSV supplementation on the inflammatory responses of broilers during heat stress. A total of 432 28-d-old white-feathered broilers (817 crossbred chicken) with an average weight of 549 ± 4 g were randomly allotted to 4 equal groups (Half male and half female, 6 replicates/group, 18 chickens/replicate), including normal temperature (NT) group (24 ± 2°C for 24 h/d, basal diet), NT+RSV group (24 ± 2°C for 24 h/d, basal diet + RSV), heat stress (HT) group (37 ± 2°C for 8 h/d, basal diet), and HT+RSV group (37 ± 2°C for 8 h/d, basal diet + RSV). Serum samples were collected on d 7 and 14 of heat stress, and thymus, spleen, jejunum, and bursa of Fabricius samples were collected and analyzed on d14. RSV treatment decreased the feed conversion ratio, partially reversed the negative alternations in body weight, average daily gain, and average daily feed intake caused by heat stress. RSV treatment also decreased the elevated levels of corticosterone on d 14, adrenocorticotropic hormone, and triiodothyronine in serum on d 7 caused by heat stress, and significantly increased the villus height to crypt depth ratio in the jejunum on d 14. Dietary RSV also reduced heat stress-induced splenic pro-inflammatory cytokine concentrations. TUNEL assay showed that RSV significantly reduced heat stress-induced the number of apoptotic cells. Remarkably, RSV down-regulated some splenic related genes for apoptosis genes, including BCL-2, Apaf-1, and MDM2 mRNA levels induced by heat stress. According to GO and KEGG enrichment analyses, the differential genes between HT and HT + RSV groups were mainly associated with immune system process, hematopoietic or lymphoid organ development, and toll-like receptor signaling pathway. The relative mRNA expression of NF-κB, heat shock protein 70 (HSP70), and p38 MAPK were markedly decreased by the combination of RSV and heat stress. These findings showed that RSV might reduce the splenic inflammatory response in heat-stressed white-feather broilers by inhibiting heat stress-induced activation of NF-B, MAPK, and HSP70, as well as inhibiting the activation of mitochondrial apoptotic pathways.

Wind power generation provides a new route for the sustainable development of energy. However, with the large scale integration of wind farms, the volatile wind energy and the correlation among various wind speeds bring a considerable quantity of uncertainty for the power system operation. In this paper, a probabilistic power flow (PPF) analysis model for the power system incorporating the correlation among various wind speeds is proposed. As distinct from existing studies, in this paper, we introduce the relevance vector machine (RVM) into correlation modeling of wind speeds via historical learning samples to construct bivariate joint distribution. Compared with the conventional parameter estimation methods, the proposed method has higher flexibility and computational efficiency. On this basis, the regular vine copula approach is adopted further to build the multivariate joint distribution model of wind speeds. To calculate the PPF of power system with the integration of wind power, we employ the three-point estimation method (3PEM) while the Rosenblatt Transformation technique is proposed to transform the input variables into independent variables. The effectiveness of the proposed calculation framework is examined through simulation studies, and the obtained results illustrate the advantages of the proposed method.

Daidzein is a plant isoflavonoid primarily isolated from Pueraria lobate Radix as the dry root of P. lobata (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China. Despite the report that daidzein can prevent neuronal damage and improve outcome in experimental stroke, the mechanisms of this neuroprotective action have been not fully elucidated. The aim of this study was to determine whether the daidzein elicits beneficial actions in a stroke model, namely, cerebral ischemia/reperfusion (I/R) injury, and to reveal the underlying neuroprotective mechanisms associated with the regulation of Akt/mTOR/BDNF signal pathway. The results showed that I/R, daidzein treatment significantly improved neurological deficits, infarct volume, and brain edema at 20 and 30 mg/kg, respectively. Meanwhile, it was found out that the pretreatment with daidzein at 20 and 30 mg/kg evidently improved striatal dopamine and its metabolite levels. In addition, daidzein treatment reduced the cleaved Caspase-3 level but enhanced the phosphorylation of Akt, BAD and mTOR. Moreover, daidzein at 30 mg/kg treatment enhanced the expression of BDNF and CREB significantly. This protective effect of daidzein was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. To sum up, our results demonstrated that daidzein could protect animals against ischemic damage through the regulation of the Akt/mTOR/BDNF channel, and the present study may facilitate the therapeutic research of stroke.

Abstract Artificial Z‐scheme, a tandem structure with two‐step excitation process, has gained significant attention in energy production and environmental remediation. By effectively connecting and matching the band‐gaps of two different photosystems, it is significant to utilize more photons for excellent photoactivity. Herein, a novel one‐photon (same energy‐two‐photon) Z‐scheme system is constructed between rGO modified boron‐nitrogen co‐doped‐WO3, and coupled CdSe quantum dots‐(QDs). The coctalyst‐0.5%RhxCr2O3(0.5RCr) modified amount‐optimized sample 6%CdSe/1%rGO3%BN‐WO3 revealed an unprecedented visible‐light driven overall‐water‐splitting to produce ≈51 µmol h−1 g−1 H2 and 25.5 µmol h−1 g−1 O2, and it remained unchanged for 5 runs in 30 h. This superior performance is ascribed to the one‐photon Z‐scheme, which simultaneously stimulates a two photocatalysts system, and enhanced charge separation as revealed by various spectroscopy techniques. The density‐functional theory is further utilized to understand the origin of this performance enhancement. This work provides a feasible strategy for constructing an efficient one‐photon Z‐scheme for practical applications.

When coronavirus disease 2019 (COVID-19) became a pandemic, one of most important questions was whether people who smoke are at more risk of COVID-19 infection. A number of clinical data have been reported in the literature so far, but controversy exists in the collection and interpretation of the data. Particularly, there is a controversial hypothesis that nicotine might be able to prevent SARS-CoV-2 infection. In the present study, motivated by the reported controversial clinical data and the controversial hypothesis, we carried out cytotoxicity assays in Vero E6 cells to examine the potential cytoprotective activity of nicotine against SARS-CoV-2 infection and demonstrated for the first time that nicotine had no significant cytoprotective activity against SARS-CoV-2 infection in these cells.

Poria cocos (P. cocos) is a traditional Chinese medicinal product with the same origin as medicine and food. It has diuretic, anti-inflammatory and liver protection properties, and has been widely used in a Chinese medicine in the treatment of Alzheimer’s disease (AD). This study was conducted to explore the activity screening, isolation of acetylcholinesterase inhibitors (AChEIs), and in vitro inhibiting effect of P. cocos. The aim was to develop a new extraction process optimization method based on the Matlab genetic algorithm combined with a traditional orthogonal experiment. Moreover, bio−affinity ultrafiltration combined with molecular docking was used to screen and evaluate the activity of the AChEIs, which were subsequently isolated and purified using high-speed counter−current chromatography (HSCCC) and semi−preparative high-performance liquid chromatography (semi−preparative HPLC). The change in acetylcholinesterase (AChE) activity was tested using an enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on AChE and explore its mechanism of action. Five potential AChEIs were screened via bio−affinity ultrafiltration. Molecular docking results showed that they had good binding affinity for the active site of AChE. Meanwhile, the five active compounds had reversible inhibitory effects on AChE: Polyporenic acid C and Tumulosic acid were non-competitive inhibitors; 3−Epidehydrotumulosic acid was a mixed inhibitor; and Pachymic acid and Dehydrotrametenolic acid were competitive inhibitors. This study provided a basis for the comprehensive utilization of P. cocos and drug development for the treatment of AD.

The uniaxial tensile behaviors of Fe-19Cr-16Mn-2Mo-0.49N and Fe-18Cr-16Mn-2Mo-0.85N high-nitrogen and nickel-free austenitic stainless steels at two strain rates of 10−2 s−1 and 10−4 s−1 were comparatively investigated. The related deformation microstructure was characterized and fracture mechanism was analyzed. The results show that the nitrogen content and strain rate both have significant effects on the tensile properties of the tested steels. As the strain rate is the same, the tested steel containing a higher nitrogen content has higher Rm and Rp0.2. However, Rm is higher at a lower strain rate and Rp0.2 is higher at a higher strain rate in the case of the same nitrogen content. The tested steel with a lower nitrogen content (0.49 wt.%N) tensioned at a lower strain rate of 10−4 s−1 obtains the highest elongation, while the tested steel with a higher nitrogen content (0.85 wt.%N) tensioned at a higher strain rate of 10−2 s−1 has the lowest elongation. The tensile plastic deformation is mainly governed by slip and twinning, affected jointly by stacking fault energy and short-range order. Dislocation slip featured by planar slip bands and twin-like bands is the main deformation structure in the tested steel containing a higher nitrogen content (0.85 wt.%N) tensioned at a lower strain rate of 10−4 s−1, whereas twinning deformation becomes more prominent with decreasing nitrogen content and increasing strain rate.

Abstract Background Cancer arises through accumulation of somatically acquired genetic mutations. An important question is to delineate the temporal order of somatic mutations during carcinogenesis, which contributes to better understanding of cancer biology and facilitates identification of new therapeutic targets. Although a number of statistical and computational methods have been proposed to estimate the temporal order of mutations, they do not account for the differences in the functional impacts of mutations and thus are likely to be obscured by the presence of passenger mutations that do not contribute to cancer progression. In addition, many methods infer the order of mutations at the gene level, which have limited power due to the low mutation rate in most genes. Results In this paper, we develop a Probabilistic Approach for estimating the Temporal Order of Pathway mutations by leveraging functional Annotations of mutations (PATOPA). PATOPA infers the order of mutations at the pathway level, wherein it uses a probabilistic method to characterize the likelihood of mutational events from different pathways occurring in a certain order. The functional impact of each mutation is incorporated to weigh more on a mutation that is more integral to tumor development. A maximum likelihood method is used to estimate parameters and infer the probability of one pathway being mutated prior to another. Simulation studies and analysis of whole exome sequencing data from The Cancer Genome Atlas (TCGA) demonstrate that PATOPA is able to accurately estimate the temporal order of pathway mutations and provides new biological insights on carcinogenesis of colorectal and lung cancers. Conclusions PATOPA provides a useful tool to estimate temporal order of mutations at the pathway level while leveraging functional annotations of mutations.

Tetraspanin CD151 is increasingly implicated as a multifaceted mediator of cancer development and progression. Here we investigated the role of CD151 in breast cancer in the context of the Wnt oncogenic activation. Our data showed that removal of one or both of CD151 alleles in the MMTV-Wnt1 model significantly decreased the tumor-free survival of mice from 34 weeks on average to 22 weeks and 18 weeks, respectively. This effect coincided with an accelerated tumor growth and an increased number of Ki-67+ proliferative cells. Mechanistically, the CD151-deficient tumors were largely ER+, and exhibited hyperactivation of the Wnt pathway as reflected by a marked upregulation in β-catenin and Cyclin D1, and their target genes. In addition, E-cadherin displayed a cytosolic distribution and transcription factor Snail was markedly upregulated. Collectively, this data implies that CD151 suppresses the Wnt1-driven tumorigenesis, at least in part, via counteracting the epithelial-mesenchymal transition (EMT)-like program in luminal epithelial cells. Meanwhile, the proportion of tumor cells expressing CK5 or p63, the biomarkers of myoepithelial/basal cells, markedly decreased in the absence of CD151. This change was accompanied by a decreased invasiveness of tumors and their incompetence to form a long-term cell culture. Consistent with this basal cell-linked role, the CD151 downregulation impairs mammosphere formation in MCF-10A cells and the defect was rescued by re-expression of intact CD151 ORF, but not its integrin binding-defective mutant. Overall, our study suggests that CD151 is a key player in the Wnt oncogene-driven tumorigenesis and impacts breast cancer malignancy in a cell type-dependent manner.

The germination of seeds and establishment of seedling are the preconditions of plant growth and are antagonistically regulated by multiple phytohormones, e.g., ethylene, abscisic acid (ABA), and gibberellic acid (GA). However, the interactions between these phytohormones and their upstream transcriptional regulation during the seed and seedling growth in rice remain poorly understood. Here, we demonstrated a rice NAC (NAM-ATAF-CUC) transcription factor, OsNAC2, the overexpression of which increases the ethylene sensitivity in rice roots during the seedling period. Further study proved that OsNAC2 directly activates the expressions of OsACO and OsACO3, enhancing ethylene synthesis, and then retards seedling establishment. Moreover, OsNAC2 delays the germination of seeds and coleoptile growth through the ABA pathway instead of the ethylene and GA pathway, by targeting the promoters of OsNCED3, OsZEP1, and OsABA8ox1. We also found that OsNAC2 regulates downstream targets in a time-dependent manner by binding to the promoter of OsKO2 in the seedling period but not in the germination stage. Our finding enriched the regulatory network of ethylene, ABA, and GA in the germination of rice seeds and seedling growth, and uncovered new insights into the difference of transcription factors in targeting their downstream components.

Summary: Dysregulation of Wnt signaling is a hallmark of many cancers, and the development of effective, non-toxic small-molecule Wnt inhibitors is desirable. Off-target toxicities of new compounds are typically tested in mouse models, which is both costly and time consuming. Here, we present a rapid and inexpensive protocol to determine the in vivo toxicity and efficacy of novel Wnt inhibitors in zebrafish using a combination of a fluorescence reporter assay as well as eye rescue and fin regeneration assays. These experiments are completed within 1 week to rapidly narrow drug candidates before moving to more expensive pre-clinical testing.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2020).

H-polarization, along with E-polarization, indicates the lateral variations of the Earth conductivity, which influence the induced electric field distribution. The coast effect is a typical H-polarization phenomenon that causes local geoelectric field enhancement in coastal areas and significantly affects the geomagnetically induced currents (GIC) distributions in power grids. The influences of H-polarization on geoelectric fields and GIC form the basis for further research on power grid disasters resulting from magnetic storms. In this paper, block and thin-shell models of the coast effect are established, and the electric field distribution in the case of H-polarization is calculated using the finite element method. The results demonstrate the effects of the conductivity, frequency, and distance from the interface of a different conductivity on electric field distortion. Additionally, the relationship between H-polarization and GIC in power grids is investigated, demonstrating that the GIC can be influenced within 100 km in the H-polarization case. The methods and results provide a theoretical basis for GIC risk assessment and development of a control strategy for the power grid.

During a magnetic storm, the induced geoelectric field drives geomagnetically induced currents (GIC) in power transmission networks, railway systems, and pipelines, negatively affecting these systems. In regions with complex geological structures, the lateral earth conductivity changes influence the induced electric field distribution in the earth. H- and E-polarization are two cases of the orientation of the E-field vector relative to the lateral changes. A model of the earth with lateral conductivity changes is established in this paper to examine the effects of conductivity change across a discontinuity on the magnitude of the E-field for the case of the E-field parallel to the discontinuity. The electric field distribution with distance from the discontinuity is calculated, and the relationship between the lateral conductivity changes and electric field distortion is analyzed using the finite element method. In addition, the GIC variation in the power grid due to the lateral conductivity changes is examined. Then, the factors affecting GIC, including conductivity, frequency, and distance, are investigated. The results show that lateral conductivity changes can influence the GIC in power lines running parallel to the discontinuity up to 250 km from the discontinuity. The methods and results are significant for understanding how lateral conductivity changes influence GIC and will improve the accuracy of GIC calculations.

During geomagnetic storms, geomagnetically induced currents (GIC) and pipe-soil potential (PSP) generated in a pipeline present a risk to the safe operation of the pipeline. An important factor affecting the size and distribution of GIC and PSP is pipeline insulation leakage points. We obtain the relationship between the resistance of leakage points, their radius, and soil conductivity through modeling and derivation and verify the reliability of this equation by simulation using ANSYS software. Then a pipeline network model including leakage points is established. The influences of different radii and locations of leakage points on GIC and PSP distributions are discussed. The results suggest that medium and even small geomagnetic storms may aggravate corrosion of pipelines and affect their safe operation. This influence is related to the distribution of leakage points, the size of leakage points, and the structure of pipelines at the leakage points. The closer the leakage point is to the end of the pipeline, the greater the impact on the GIC distribution. The larger the radius of the pipeline leakage point, the greater the influence of the leakage point on the GIC distribution of the pipeline. The presence of branches at the leakage points can reduce the influence of leakage points on GIC and PSP distributions.

In this study, an advanced Internet of Things (IoT) technology is applied to the energy management of an intelligent combined cooling, heating, and power (CCHP) commercial building system. Based on the framework of a smart energy management system (SEMS) using IoT technology, a two-stage optimal scheduling model is proposed to determine the most economic CCHP commercial building system integrated with a three-way valve. In the day-ahead scheduling stage, the schedule is planned using the lowest operating costs of the system. In the real-time correction stage, the correction strategy employs minimum adjustment of the output of each unit. Moreover, the schedule plan is corrected to smooth out fluctuations in the loads and renewable energy resources (RES) in a timely manner to better absorb green energy. The day-ahead scheduling model is a large-scale mixed integer nonlinear programming (MINLP) problem solved through a linearization method proposed in this study and the mixed integer linear programming method. The real-time correction optimization model is a nonlinear programming problem solved by the quantum genetic algorithm (QGA). A case study is employed to demonstrate that the IoT-based SEMS improves the system automation energy management level and user comfort. Furthermore, the proposed system structure can significantly reduce system operating costs and improve the utilization of waste heat from the internal combustion engine. In conclusion, the economic and environmental superiority of the two-stage optimal dispatch model is verified.

With the rapid growth of the economy and population, the desire to use groundwater supplies is increasing. In order to detect groundwater, conducting a geophysics survey is a common way to map the subsurface. This method can describe the subsurface’s physical properties. For example, the direct current (DC) resistivity method provides a resistivity map of the subsurface, in which the groundwater is normally located in low resistivity anomaly zones. However, the DC method needs to overcome the challenges of the urban environment, with its infrastructure and background noise. In this paper, we propose a pseudo-3D resistivity surveying method to solve these problems, and it is applied to situations of groundwater detection within the city environment, dam leakage, and drinking water. From the pseudo-3D resistivity surveying, we detected the low-resistivity anomaly in the area, which is interpreted as groundwater through borehole verification.

Summary: Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3's lysine 9 (H3K9Me2), a repressive marker for transcription. Inhibiting KDM3 increased H3K9Me2 levels, repressed Wnt target genes, and curtailed in vitro CRC cell proliferation. CBA-1 also exhibited in vivo inhibition of Wnt signaling in a zebrafish model without displaying in vivo toxicity.

The Tianshui-Sunjiaxia area is located in the connection zone of West Qinling Orogen and North Qilian Orogen, which could provide great insights into the amalgamation processes between the northern and southern blocks of China. Three subduction- and rift-related rocks gneissic granite from North Qilian arc-interarc belt (NQAI) granite and metabasalt from North Qinling back-arc basin (NQBA) are distinguished across the connection zone. The gneissic granite was generated by melts from older crustal materials of Longshan Group with the addition of a relatively juvenile basaltic source from the lower crust during the collision process. The Liwanxincun metabasalt reflects the mixing of the partial melting of the shallow asthenospheric mantle and the metasomatized mantle in a back-arc extension setting. The LA-ICP-MS zircon U-Pb dating of gneissic granite (068, 069) yields crystallization ages of 457.0 ± 1.6 Ma and 445.9 ± 2.1 Ma. The study area is divided into six tectonic units in Early Paleozoic time involving NQAI (Yanjiadian-Xinjie) continental arc, interarc rift basin (Maojiamo-Xiwali), continental arc (Chenjiahe-Wangjiacha); NQBA back-arc rift basin (Huluhe-Hongtubao), island arc and ophiolitic melange belt (North Qinling-Shangdan). A tectonic model is proposed in which the NQAI continental arc (Yanjiadian-Xinjie) might represent the early period of subduction of North Qilian Ocean (NQO) and the interarc rift is the product of the extension triggered by southward subduction of NQO. The ongoing subduction of NQO then leads to the formation of Chenjiahe-Wangjiacha continental arc, as well as the Hongtubao back-arc spreading ridge in NQBA back-arc basin (Huluhe). The tectonic evolution of the connection zone is closely associated with the closure of the North Qilian Ocean and North Qinling-Shangdan Ocean in the context of the convergence process of micro-continental blocks, including North China block, Longshan group and North Qinling Terrane.

[This corrects the article DOI: 10.1371/journal.pone.0099741.].

Abstract Background Hazel (Corylus spp.) exhibits ovary differentiation and development that is initiated from the ovary primordium after pollination, conferring the plant with a unique delayed fertilization. Failure of development of the ovary and ovule after pollination can lead to ovary abortion and blank fruit formation, respectively, with consequent yield loss. However, the genes involved in ovary and ovule differentiation and development are largely unknown. Results In unpollinated pistillate inflorescences (stage F), the stigma shows an extension growth pattern. After pollination, a rudimentary ovary begins to form (stage S), followed by ovule differentiation (stage T) and growth (stage FO). Total RNA was obtained from pistillate inflorescences or young ovaries at stage F, S, T and FO, and sequencing was carried out on a HiSeq 4000 system. De novo assembly of sequencing data yielded 62.58 Gb of nucleotides and 90,726 unigenes; 5524, 3468, and 8714 differentially expressed transcripts were identified in F-vs-S, S-vs-T, and T-vs-FO paired comparisons, respectively. An analysis of F-vs-S, S-vs-T, and T-vs-FO paired comparisons based on annotations in the Kyoto Encyclopedia of Genes and Genomes revealed six pathways that were significantly enriched during ovary differentiation, including ko04075 (Plant hormone signal transduction). Auxin level increased after pollination, and an immunohistochemical analysis indicated that auxin was enriched at the growth center of pistillate inflorescences and young ovaries. These results indicate that genes related to auxin biosynthesis, transport, signaling, the floral quartet model, and flower development may regulate ovary and ovule differentiation and development in hazel. Conclusions Our findings provide insight into the molecular mechanisms of ovary differentiation and development after pollination in this economically valuable plant.