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Batch scheduling is a crucial part of pipeline enterprise operation management, especially in the context of market-oriented operation. It involves 3 main tasks: quickly preparing batch plans, accurately tracking interface movement, and operation condition in real time. Normally, the completion of multi-product pipeline batch scheduling depends on simulation models or optimization models and corresponding conventional solving algorithm. However, this approach becomes inefficient when applied to large-scale systems. The rapid development of machine learning has brought new ideas to batch scheduling research. This paper first reviews the current state of batch scheduling technology, and suggests that applying machine learning to it is a promising development direction. Then, we summarize the progress of machine learning applications in batch planning, interface movement tracking, and operational condition monitoring, and point out their limitations. Finally, considering the separation of refined oil production, transportation, and sales processes, 5 recommendations are put forward: oil supply and demand prediction and pipeline capacity prediction, batch planning, batch interface movement tracking, mixed oil development monitoring, and pipeline operation condition identification.

Abstract A topological insulator is a quantum material which possesses conducting surfaces and an insulating bulk. Despite extensive researches on the properties of Dirac surface states, the characteristics of bulk states have remained largely unexplored. Here we report the observation of spinor-dominated magnetoresistance anomalies in β-Ag2Se, induced by a magnetic-field-driven band topological phase transition. These anomalies are caused by intrinsic orthogonality in the wave-function spinors of the last Landau bands of the bulk states, in which backscattering is strictly forbidden during a band topological phase transition. This new type of longitudinal magnetoresistance, purely controlled by the wave-function spinors of the last Landau bands, highlights a unique signature of electrical transport around the band topological phase transition. With further reducing the quantum limit and gap size in β-Ag2Se, our results may also suggest possible device applications based on this spinor-dominated mechanism and signify a rare case where topology enters the realm of magnetoresistance control.

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Due to differences in raw materials and production processes, different spirits exhibit various flavor even if undergo distillation operation. In this study, sensory analysis could clearly distinguish 5 types spirits, and had been validated through quantitative targeted flavoromics analysis. Consequently, 44 potential differential markers between 5 types spirits were screened. Among, 34 definite differential markers were further confirmed to be highly correlated with target sensory attributes and could effectively distinguish types of spirits. Ultimately, 14 key differential markers (including 2-methylbutane, linalool, acetaldehyde, d-limonene, β-myrcene, phenylethyl alcohol, phenethyl acetate, heptyl formate, ethyl octanoate, ethyl decanoate, ethyl pentanoate, ethyl hexanoate, hexanoic acid, and ethyl hexadecanoate) could reveal the chemical sources of spirit sensory and serve as targets for identifying different types of spirits. Overall, the results of flavoromic characterization of 5 types spirits provided a significant step forwards in understanding of differentiation of spirits by sensory coupled with quantitative, and statistical analysis

Abstract Background The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration. Methods The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1). Results Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly. Conclusion Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function. Graphical Abstract Tet2 interacts with Stat1 in the cytoplasm and suppresses IFN-γ-induced macrophage activation. Tet2 inhibitor decreases the combination of Stat1 and Tet2, activating the macrophages through the Jak-Stat pathway. The activation of macrophages increases the transcription and translation of the IL-6 and promotes liver regeneration. Video Abstract

Abstract Background Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. Methods We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. Results We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. Conclusions Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.

Baijiu is popular with a long history and balanced flavor. Flavor type is the most widely used classification mode for Baijiu. However, the evolutionary relationships of Baijiu flavor types and the differential markers between flavor types are still unclear, significantly impacting the development of the Baijiu industry. In this study, a total of 319 trace components were identified using gas chromatography–olfactometry–mass spectrometry and gas chromatography–mass spectrometry. Among them, 91 trace components with high odor active values or taste active values were recognized as flavor components. Then random forests were conducted to screen differential markers between the derived and basic flavor types, while a principal component analysis assessed their effectiveness in distinguishing the flavor types of Baijiu. Finally, 19 differential markers (including 3-methylbutyric acid, pentanoic acid, 2-butanol, 2,3-butanediol, ethyl pro-panoate, isobutyl acetate, ethyl butanoate, ethyl hexanoate, ethyl heptanoate, ethyl lactate, ethyl 2-hydroxy butanoate, isopentyl hexanoate, ethyl nonanoate, isopropyl myristate, ethyl tetradecanoate, ethyl benzoate, 2,4-di-t-butylphenol, 2-methylbutanal and 3-octanone) were screened and proven to effectively reveal the evolution of Baijiu flavor types; these were further verified as key differential markers using addition tests and a correlation analysis.

Abstract Background The three‐dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored. Methods We employed Hi‐C and RNA‐seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns. Results We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi‐C and RNA‐seq data demonstrated that changes inhigher‐order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/β‐Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT‐PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro. Conclusion Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.

Structures of E. coli threonyl-tRNA synthetase in complex with natural product obafluorin (OB) reveal that OB is a unique covalent inhibitor.

Abstract Introduction Low‐grade gliomas (LGGs) are currently considered a premalignant condition for high‐grade gliomas (HGGs) and are characterized by a relatively intact immune system. Immunotherapeutic modalities may offer a safe and effective treatment option for these patients. However, the CD2–CD58 axis, an important component of the immunological synapse, remains unknown in LGG. Methods RNA‐seq data from TCGA databases were analyzed. Immune cell infiltration was determined using a single‐sample gene set enrichment analysis (ssGSEA) based on integrated immune gene sets from published studies. Kaplan–Meier survival analysis, univariate and multivariate logistic analysis, and the ESTIMATE algorithm were employed to evaluate the impact of the CD2–CD58 axis on adult LGG patients. Results The expression of the CD2–CD58 axis was found to be elevated with increasing of WHO grade (p

Abstract To protect the satellite communication uplink signal (SCUS) from being intercepted by an eavesdropper, this study proposes several tactics to ensure SCUS being in the low probability of intercept (LPI) state. First, based on the satellite link equation, an optimisation model for LPI SCUS is established with coding and synchronisation of symbol and carrier frequency. However, when the satellite is on the synchronisation orbit, the LPI model of SCUS is still very likely to be intercepted by an eavesdropper that might be close to the SCUS. Aiming at this problem, the second tactic is to mask LPI SCUS with directed and power limited jamming. The purpose of using directed and power limited jamming is to reduce direction‐finding accuracy of the eavesdropper, and to achieve the optimal LPI performance with the minimum radiation energy. The high‐order cumulate algorithm is used to predict the signal‐to‐noise ratio of mixed signal in the second tactic. The simulation results show that the model of LPI SCUS can effectively reduce the detection probability compared with the traditional satellite uplink signals, and the second tactic can effectively reduce the direction‐finding accuracy of the SCUS by the eavesdropper.

In this paper, we consider stochastic approximation algorithms for least-square and logistic regression with no strong-convexity assumption on the convex loss functions. We develop two algorithms with varied step-size motivated by the accelerated gradient algorithm which is initiated for convex stochastic programming. We analyse the developed algorithms that achieve a rate of $ O(1/n^{2}) $ where $ n $ is the number of samples, which is tighter than the best convergence rate $ O(1/n) $ achieved so far on non-strongly-convex stochastic approximation with constant-step-size, for classic supervised learning problems. Our analysis is based on a non-asymptotic analysis of the empirical risk (in expectation) with less assumptions that existing analysis results. It does not require the finite-dimensionality assumption and the Lipschitz condition. We carry out controlled experiments on synthetic and some standard machine learning data sets. Empirical results justify our theoretical analysis and show a faster convergence rate than existing other methods.

Abstract Background Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1 R625H ), but its functional effects and underlying molecular mechanisms remain largely unexplored. Methods Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1 R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1 R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA. Results Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1 R625H allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1R625H promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1R625H and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway. Conclusions Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1 R625H mutation.

Adult language learners show distinct abilities in acquiring a new language, yet the underlying neural mechanisms remain elusive. Previous studies suggested that resting-state brain connectome may contribute to individual differences in learning ability. Here, we recorded electroencephalography (EEG) in a large cohort of 106 healthy young adults (50 males) and examined the associations between resting-state alpha band (8–12 Hz) connectome and individual learning ability during novel word learning, a key component of new language acquisition. Behavioral data revealed robust individual differences in the performance of the novel word learning task, which correlated with their performance in the language aptitude test. EEG data showed that individual resting-state alpha band coherence between occipital and frontal regions positively correlated with differential word learning performance (p = 0.001). The significant positive correlations between resting-state occipito-frontal alpha connectome and differential world learning ability were replicated in an independent cohort of 35 healthy adults. These findings support the key role of occipito-frontal network in novel word learning and suggest that resting-state EEG connectome may be a reliable marker for individual ability during new language learning.

The storage process of Baijiu is an integral part of its production (the quality undergoes substantial changes during the aging process of Baijiu). As the storage time extends, the flavor compounds in Baijiu tend to undergo coordinated transformation, thereby enhancing the quality of Baijiu. Among them, long-chain fatty acid ethyl esters (LCFAEEs) were widely distributed in Baijiu and have been shown to have potential contributions to the quality of Baijiu. However, the current research on LCFAEEs in Baijiu predominantly focuses on the olfactory sensation aspect, while there is a lack of systematic investigation into their influence on taste and evaluation after drinking Baijiu during the aging process. In light of this, the present study investigates the distribution of LCFAEEs in Baijiu over different years. We have combined modern flavor sensory analysis with multivariate chemometrics to comprehensively and objectively explore the influence of LCFAEEs on Baijiu quality. The results demonstrate a significant positive correlation between the concentration of LCFAEEs and the fruity aroma (p < 0.05, r = 0.755) as well as the aged aroma (p < 0.05, r = 0.833) of Baijiu within a specific range; they can effectively reduce the off-flavors and spicy sensation of Baijiu. Furthermore, additional experiments utilizing a single variable suggest that LCFAEEs were crucial factors influencing the flavor of Baijiu, with Ethyl Palmitate (EP) being the most notable LCFAEE that merits further systematic investigation.

Background and Objectives: The diagnosis and treatment of pituitary adenomas with cavernous sinus invasion pose significant challenges for clinicians. The objective of this study is to investigate the expression profile and prognostic value of HSPB1 (heat shock protein beta-1) in pituitary adenomas with invasive and non-invasive features. Additionally, we aim to explore the potential relationship between HSPB1 expression and immunological functions in pituitary adenoma. Materials and Methods: A total of 159 pituitary adenoma specimens (73 invasive tumours and 86 non-invasive tumours) underwent whole-transcriptome sequencing. Differentially expressed genes and pathways in invasive and non-invasive tumours were analysed. HSPB1 was subjected to adequate bioinformatics analysis using various databases such as TIMER, Xiantao and TISIDB. We investigated the correlation between HSPB1 expression and immune infiltration in cancers and predicted the target drug of HSPB1 using the TISIDB database. Results: HSPB1 expression was upregulated in invasive pituitary adenomas and affected immune cell infiltration. HSPB1 was significantly highly expressed in most tumours compared to normal tissues. High expression of HSPB1 was significantly associated with poorer overall survival. HSPB1 was involved in the regulation of the immune system in most cancers. The drugs DB11638, DB06094 and DB12695 could act as inhibitors of HSPB1. Conclusions: HSPB1 may serve as an important marker for invasive pituitary adenomas and promote tumour progression by modulating the immune system. Inhibitors of HSPB1 expression are currently available, making it a potential target for therapy in invasive pituitary adenoma.

Abstract Vigorous development of electric vehicles is one way to achieve global carbon reduction goals. However, fires caused by thermal runaway of the power battery has seriously hindered large‐scale development. Adding thermal runaway retardants (TRRs) to electrolytes is an effective way to improve battery safety, but it often reduces electrochemical performance. Therefore, it is difficult to apply in practice. TRR encapsulation is inspired by the core–shell structures such as cells, seeds, eggs, and fruits in nature. In these natural products, the shell isolates the core from the outside, and has to break as needed to expose the core, such as in seed germination, chicken hatching, etc. Similarly, TRR encapsulation avoids direct contact between the TRR and the electrolyte, so it does not affect the electrochemical performance of the battery during normal operation. When lithium‐ion battery (LIB) thermal runaway occurs, the capsules release TRRs to slow down and even prevent further thermal runaway. This review aims to summarize the fundamentals of bioinspired TRR capsules and highlight recent key progress in LIBs with TRR capsules to improve LIB safety. It is anticipated that this review will inspire further improvement in battery safety, especially for emerging LIBs with high‐electrochemical performance.

Abstract Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug‐resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole‐resistant C. auris strains, with MICs of 4–16 µg/ml. The drug‐like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre‐clinical evaluation.

In this study, we developed a simple strategy to prepare a biofilm reactor (BFR) sensor for the universal biochemical oxygen demand (BOD) determination. The microorganisms in fresh water were domesticated by artificial seawater with different salinity gradients successively to prepare the BFR sensor. The prepared BFR sensor exhibits an efficient ability to degrade a variety of organic substances. The linear range of BOD determination by the BFR sensor is 1.0–10.0 mg/L−1 with a correlation coefficient of 0.9951. The detection limit is 0.30 mg/L according to three times of signal-to-noise ratio. What is more, the BFR sensor displayed excellent performances for the BOD determination of different water samples, including both fresh water and seawater. The 16S-rRNA gene sequencing technology was used to analyze the microbial species before and after the domestication. The results show that it is a general approach for the rapid BOD determination in different water samples.

Renewable energy has the characteristics of low carbon and environmental protection compared to traditional water and thermal power, but it also has the intermittency and uncertainty that traditional water and thermal power does not have. These characteristics make the inertia of the power system increase, which greatly affects the frequency stability of the grid. To solve such problems, the participation of demand-side resources (DSRs) in the dispatch of power systems has become a viable solution.However, unlike generation-side resources, DSRs have their own unique characteristics. In this paper, by taking into account a load frequency control system (LFC) with intermittent demand-side resources, the robust H∞ load frequency control problem are discussed in detail.A robust controller to coordinate the load side with the resource side is introduced. A critical stability criterion and robust performance evaluation of the new LFC system was carried out. Finally, simulation results based on the new LFC system are provided to demonstrate that the proposed control strategy can effectively improve the stability and robustness of the grid under large disturbances, thus allowing the grid frequency to return to the reference value.

Pituitary adenomas (PAs) are a neoplastic proliferation of anterior pituitary. Signature of Notch pathway relies upon the histopathological type of PAs. The details of Notch pathway that are involved in the migration and invasion of Pas are still unclear. This paper filters and testifies the relation between Notch signaling pathway and the migration/invasion in subtypes of PAs. The diversity of genes and pathways is investigated based on transcriptome data of 60 patients by KEGG pathway analysis and GSEA. A series of functional experiments demonstrate the role of candidate genes by overexpression and antibody blocking in GH3 cell line. Volcano map and GSEA results exhibit the differential and the priority of Jagged1 canonical Notch Ligand (JAG1) in the Notch pathway combined with clinical features. JAG1 is involved in epithelial–mesenchymal transition (EMT) in PAs by correlation analysis of RNA-seq data. Progression-free survival (PFS) of patients with high JAG1 was shorter than patients with low JAG1 according to follow-up data (P = 0.006). Furthermore, overexpression and antibody blocking experiments in GH3 cell line indicate that JAG1 could promote cell proliferation, migration, and G1/S transition. Double luciferase reporter assay gives manifests that JAG1 is the target gene of miR-424-3p, and mimics or inhibitor of miR-424-3p can regulate the level of JAG1 which, in turn, affects cell proliferation and the levels of MMP2 and VIM in GH3 cell line, respectively. Our study delves into the relation between the Notch signaling pathway and cell proliferation and EMT in PAs, providing a potential treatment through targeting JAG1.

For the benefit from accurate electricity price forecasting, not only can various electricity market stakeholders make proper decisions to gain profit in a competitive environment, but also power system stability can be improved. Nevertheless, because of the high volatility and uncertainty, it is an essential challenge to accurately forecast the electricity price. Considering that recurrent neural networks (RNNs) are suitable for processing time series data, in this paper, we propose a bidirectional long short-term memory (LSTM)-based forecasting model, BRIM, which splits the state neurons of a regular RNN into two parts: the forward states (using the historical electricity price information) are designed for processing the data in positive time direction and backward states (using the future price information available at inter-connected markets) for the data in negative time direction. Moreover, due to the fact that inter-connected power exchange markets show a common trend for other neighboring markets and can provide signaling information for each other, it is sensible to incorporate and exploit the impact of the neighboring markets on forecasting accuracy of electricity price. Specifically, future electricity prices of the interconnected market are utilized both as input features for forward LSTM and backward LSTM. By testing on day-ahead electricity prices in the European Power Exchange (EPEX), the experimental results show the superiority of the proposed method BRIM in enhancing predictive accuracy in comparison with the various benchmarks, and moreover Diebold-Mariano (DM) shows that the forecast accuracy of BRIM is not equal to other forecasting models, and thus indirectly demonstrates that BRIM statistically significantly outperforms other schemes.

Fused polyheterocyclic derivatives are available by annulation of a tetramate scaffold, and been shown to have antibacterial activity against a Gram-negative, but not a Gram-positive, bacterial strain. While the activity is not potent, these systems are structurally novel showing, in particular, a high level of polarity, and offer potential for the optimization of antibacterial activity.