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Cholangiocarcinoma is the second most common primary liver cancer, and its global incidence has increased in recent years. Radical surgical resection and systemic chemotherapy have traditionally been the standard treatment options. However, the complexity of cholangiocarcinoma subtypes often presents a challenge for early diagnosis. Additionally, high recurrence rates following radical treatment and resistance to late-stage chemotherapy limit the benefits for patients. Immunotherapy has emerged as an effective strategy for treating various types of cancer, and has shown efficacy when combined with chemotherapy for cholangiocarcinoma. Current immunotherapies targeting cholangiocarcinoma have predominantly focused on T lymphocytes within the tumor microenvironment, and new immunotherapies have yielded unsatisfactory results in clinical trials. Therefore, it is essential to achieve a comprehensive understanding of the unique tumor microenvironment of cholangiocarcinoma and the pivotal role of T lymphocytes within it. In this review, we describe the heterogeneous immune landscape and intercellular communication in cholangiocarcinoma and summarize the specific distribution of T lymphocytes. Finally, we review potential immune checkpoints in cholangiocarcinoma.

BackgroundElevated evidence suggests that KIF20A plays an important role in hepatocellular carcinoma (HCC) progression. Nevertheless, the underlying mechanism by which KIF20A promotes HCC cell growth are not well understood.MethodsUsing TCGA-LIHC RNAseq and GEO datasets, we assessed the KIF20A expression and patient survival in HCC and hepatitis B virus (HBV)-related HCC. Mutant and CNV analysis were performed to evaluate the genetic alteration of KIF20A in HCC. PPI network and GSEA enrichment was utilized for analyzing the KIF20A-related genes and involved pathways in HCC. To further explore regulatory mechanism in HBV-related HCC, PROMO prediction and luciferase reporter system was utilized for verifying HBx/GATA2/KIF20A binding sites. CCK-8 and flow cytometry were carried out to determine the regulation of GATA2-KIF20A on HBV-related HCC cell proliferation and apoptosis.ResultsKIF20A was significantly upregulated in pan-cancer (including HCC). KIF20A mRNA level was a significant independent predictor of overall survival in HBV-related HCC patients. Genetic alterations analysis revealed the copy number gain and amplification triggered KIF20A upregulation in HCC. In addition, the genes associated with KIF20A expression in HCC was enriched in PLK1 pathway and cell cycle in HCC. HBx might indirectly binds to KIF20A promoter via regulating GATA2. Additionally, transcription factor GATA2 directly binds to the promoter region of KIF20A. Overexpression of GATA2 promotes HepG2.2.15 cell growth and inhibits cell apoptosis via modulating KIF20A.ConclusionsOur findings demonstrated that HBx contributed to cell proliferation by interacting with GATA2 and KIF20A in HBV-related HCC.

Line-commutated converter-based high voltage direct current transmission (LCC-HVDC) has been widely applied worldwide due to its great advantages in realizing long-distance and large-capacity power transmission. However, it may also lead to instability problems, including subsynchronous torsional interaction (SSTI). This destructive phenomenon greatly threatens the safe and stable operation of power systems and has been widely concerned since the 1970 s. Existing literature has found that SSTI is caused by DC current control of rectifier station. However, the physical mechanism of this phenomenon has not been clarified clearly, which hampers further understanding of how negative damping is generated and whether it is evitable. To fill this gap, the physical process of SSTI caused by LCC-HVDC is clarified through the perspective of vector synchronization. Based on this, the negative damping mechanism is revealed. The influence of control on damping is also studied with the contribution of different control loops quantified. All results are verified through time-domain simulations and damping torque analysis.

Southern Xinjiang region represents a prototypical oasis agricultural area, and cotton is the primary cash crop. The current cotton water productivity for this area remains room for improvement. In order to refine cotton drip irrigation strategy in Southern Xinjiang, this study combined field experiment with crop model simulation and prediction. In this experiment, two irrigation methods, furrow irrigation and drip irrigation, and different degrees of deficit irrigation were set up. The impacts of soil moisture on cotton yield and quality were assessed, with the additional utilization of the Root Zone Water Quality Model (RZWQM2) for simulating irrigation scenarios and predicting cotton yield field data showed that during the 2021–2022 growing season, drip irrigation significantly increased boll weight, yield, and Water Productivity compared to furrow irrigation. The deficit irrigation with 90 % of full irrigation during the flowering period resulted in the highest yield among all drip irrigation treatments, while simultaneously improving the fiber quality. The RZWQM2 model was calibrated and validated using 2021 and 2022 cotton field experimental data, respectively. The calibrated and verified RZWQM2 model shows good performance. In terms of soil water storage, cotton yield and evapotranspiration. The simulated value output by the model is close to the measured value in the field. Model prediction data suggest that there is still room for improvement in cotton yield, accompanied by an increase in evapotranspiration. But deficit irrigation below 80 % of the full irrigation quotas poses a notable risk of yield reduction. Targeting higher yields, the predicted scenario suggests an increase in water application (irrigation quota:314.8 mm). Additionally, this study proposes irrigation regimes with water savings of 10 % and 20 %, with irrigation quotas of 290.5 mm and 266.5 mm during the growth period, respectively. Based on this study, we provide a more detailed and reliable water-saving scheme for cotton drip irrigation in southern Xinjiang region.

Relaxor ferroelectric film capacitors exhibit high power density with ultra-fast charge and discharge rates, making them highly advantageous for consumer electronics and advanced pulse power supplies. The Aurivillius-phase bismuth layered ferroelectric films can effectively achieve a high breakdown electric field due to their unique insulating layer ((Bi2O2)2+ layer)). However, designing and fabricating Aurivillius-phase bismuth layer relaxor ferroelectric films with optimal energy storage characteristics is challenging due to their inherently stable ferroelectric properties. In this work, lead-free CaBi4-xLaxTi4O15 films were synthesized using the sol–gel technique and a weakly coupled relaxor design. On one hand, the introduction of La3+ ions weaken the dipole–dipole interactions, thereby enhancing the relaxor behavior. Alternatively, the expansion of grain size is restricted to enhance the number of grain boundaries, which possess improved insulating properties. This leads to a higher breakdown electric field. The results indicate that CaBi4-xLaxTi4O15 (x = 1.0) films exhibit excellent recoverable energy storage density (70 J/cm3) and high energy efficiency (73%). Moreover, the film exhibited good temperature stability and frequency stability. This study not only identifies a promising material for dielectric film capacitors but also demonstrates that the energy storage capabilities of Aurivillius-phase bismuth layer ferroelectric films can be effectively modulated through a design incorporating weakly coupled relaxor characteristics.

The installed capacity of renewable energy generation has continued to grow rapidly in recent years along with the global energy transition towards a 100% renewable-based power system. At the same time, the grid-connected large-scale renewable energy brings significant challenges to the safe and stable operation of the power system due to the loss of synchronous machines. Therefore, self-synchronous wind turbines have attracted wide attention from both academia and industry. However, the understanding of the physical operation mechanisms of self-synchronous wind turbines is not clear. In particular, the transient characteristics and dynamic processes of wind turbines are fuzzy in the presence of grid disturbances. Furthermore, it is difficult to design an adaptive fault ride-through (FRT) control strategy. Thus, a dual-mode switching FRT control strategy for self-synchronous wind turbines is developed. Two FRT control strategies are used. In one strategy, the amplitude and phase of the internal potential are directly calculated according to the voltage drop when a minor grid fault occurs. The other dual-mode switching control strategy in the presence of a deep grid fault includes three parts: vector control during the grid fault, fault recovery vector control, and self-synchronous control. The proposed control strategy can significantly mitigate transient overvoltage, overcurrent, and multifrequency oscillation, thereby resulting in enhanced transient stability. Finally, simulation results are provided to validate the proposed control strategy.

With the continuous improvement of the penetration level of wind power in the power system, the grid-forming mode of wind turbine will gradually become one of the main modes of system synchronization. The power electronic equipment based on grid-forming control has the ability of frequency dynamic regulation, reactive power voltage regulation, weak current network operation stability and island operation similar to the conventional synchronous generator, however, the problem of strong electromagnetic stress faced by power electronic equipment under grid-forming control will be the key factor restricting the wide application and promotion of grid-forming technology. In particular, the fault ride through problem of the wind turbine under the grid-forming control will face more severe challenges. This paper is based on a switched fault ride through strategy, that is, in case of power grid fault, it is quickly converted from grid-forming control under normal working conditions to the conventional current vector control, so as to facilitate fault current limiting and realize fast dynamic reactive power support. In this paper, a fault ride through optimization control strategy of grid-forming wind turbine is proposed. During the fault, the threshold setting of entering/ exiting the fault ride through control is optimized to form hysteresis control, so as to improve the switching misoperation of control strategy caused by the large fluctuation of grid voltage in the process of fault. Finally, simulation results show that the earlier switching back to the grid-forming control is not the more conducive to the stability of the system, and there is an optimal switching time. The results verify the proposed strategy can effectively improve the transient stability of power system with grid-forming mode of the wind turbine.

IntroductionControversies surround the issue if chronic consumption of a high-sugar diet is detrimental to health or not. This study investigates whether lifelong consumption of a higher sucrose diet will induce overeating, and obesity, and cause metabolic dysfunctions such as hyperglycemia and dyslipidaemia in C57BL/6N mice, compared to a lower sucrose diet.MethodsMale C57BL/6N mice at 3 weeks of age were randomized into consuming a diet with 25 or 10% kcal from sucrose for the rest of their lives. Body weight, food and water intake, fasting blood glucose, insulin, and lipid levels were measured at regular intervals. At the end of the study, organs and tissues were collected and gene expression was measured.ResultsThere was no discernible difference in the impact on food intake, body composition, glucose and lipid homeostasis, liver triglyceride content, life expectancy, as well as gene expression related to intermediary metabolism between mice fed a diet with 10 vs. 25% kcal as sucrose over their lifespan. We also showed that switching from a 25% kcal diet to a 10% kcal diet at different life stages, or vice versa, did not appear to affect these outcomes of interest.DiscussionThe results from our study suggest that lifelong consumption of a higher sugar diet generally did not induce overeating and obesity, disrupt carbohydrate metabolism and lipid homeostasis, and reduce life expectancy compared with a lower sugar diet. Our unorthodox findings disagreed with the popular belief that higher sugar consumption is detrimental to health, which should be confirmed in future studies.

This study addresses the analysis of complex multivariate survival data, where each individual may experience multiple events and a wide range of relevant covariates are available. We propose an advanced modeling approach that extends the classical shared frailty framework to account for within-subject dependence. Our model incorporates a flexible frailty distribution, encompassing well-known distributions, such as gamma, log-normal, and inverse Gaussian. To ensure accurate estimation and effective model selection, we utilize innovative regularization techniques. The proposed methodology exhibits desirable theoretical properties and has been validated through comprehensive simulation studies. Additionally, we apply the approach to real-world data from the Medical Information Mart for Intensive Care (MIMIC-III) dataset, demonstrating its practical utility in analyzing complex survival data structures.

Biofouling poses considerable technical challenges to agricultural irrigation systems. Controlling biofouling with strong chemical biocides is not only expensive and sometimes ineffective, but also contributes to environmental pollution. This study investigated the application of nanobubbles (NBs) on minimizing biofouling in agricultural irrigation water pipelines. Treatment performances were assessed using low concentration bubbles (LCB) and high concentration bubbles (HCB) together with a negative control (CK: no-NBs). 16 s rRNA gene sequencing and X-ray diffraction were used to characterize the microbial community and mineral compositions of biofilms in water emitters. Results demonstrated that NBs effectively mitigated biofouling through reducing fixed-biomass by 31.3−52.1%. A significantly different microbial composition was found in the biofilm community with reduced biodiversity. Molecular ecological network analysis revealed that NBs were detrimental to the mutualistic interactions among microbial species – destabilizing the network complexity and size, which was expressed as decreasing in extracellular polymers and biofilm biomass. Furthermore, NBs significantly decreased the deposition of carbonate, silicate, phosphate, and quartz on the pipe surfaces, leading to reductions of total content of minerals in biofilms. Therefore, this study demonstrated that NBs treatment could be an effective, and eco-friendly solution for biofouling control in agricultural water distribution systems.

In the past decade, strong coupling between light and matter has transitioned from a theoretical idea to an experimental reality. This represents a new field of quantum light–matter interaction, which makes the coupling strength comparable to the transition frequencies in the system. In addition, the achievement of multimode strong coupling has led to such applications as quantum information processing, lasers, and quantum sensors. This paper introduces the theoretical principle of multimode strong coupling based on surface plasmons and reviews the research related to the multimode interactions between light and matter. Perspectives on the future development of plasmonic multimode coupling are also discussed.

Motivated by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, the objective of integration of important biomarkers for the early detection of Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) as a therapeutic intervention is most likely to be beneficial in the early stages of disease progression. Developing predictors for MCI to AD comes down to genotype variables such that the dimension of predictors increases as the sample becomes large. Thus, we consider the sparsity concept of coefficients in a high-dimensional regression model with clustered failure time data such as ADNI, which enables enhancing predictive performances and facilitates the model’s interpretability. In this study, we propose two MM algorithms (profile and non-profile) for the shared frailty survival model firstly and then extend the two proposed MM algorithms to regularized estimation in sparse high-dimensional regression model. The convergence properties of our proposed estimators are also established. Furthermore simulation studies and analysis of ADNI data are illustrated by our proposed methods.

Recently, telemedicine solutions have become a new trend in remote medical treatment. Many diseases are originated from abnormal variation of biological processes, especially in nucleosome positioning. Thus, effective prediction of nucleosome positioning becomes a hotspot in the research of telemedicine. In this paper, a novel method is provided to compare varies of sequences firstly. This method, which is called fractal entropy increment of diversity (FEID), is based on information entropy and increment of diversity. Then, a novel nucleosome positioning method is provided by using FEID into the data set of diversiform DNA sequences of human, worm, fly, and yeast. Moreover, experimental results show that FEID is an effective nucleosome positioning method by compared with other methods on several benchmark data sets. Finally, the most important nucleotide sequence in nucleosome positioning is provided based on calculated contribution rates of nucleotide sequences.

Transcription factors have traditionally been viewed with skepticism as viable drug targets, but they offer the potential for completely novel mechanisms of action that could more effectively address the stem cell like properties, such as self-renewal and chemo-resistance, that lead to the failure of traditional chemotherapy approaches. Core binding factor is a heterodimeric transcription factor comprised of one of 3 RUNX proteins (RUNX1-3) and a CBFβ binding partner. CBFβ enhances DNA binding of RUNX subunits by relieving auto-inhibition. Both RUNX1 and CBFβ are frequently mutated in human leukemia. More recently, RUNX proteins have been shown to be key players in epithelial cancers, suggesting the targeting of this pathway could have broad utility. In order to test this, we developed small molecules which bind to CBFβ and inhibit its binding to RUNX. Treatment with these inhibitors reduces binding of RUNX1 to target genes, alters the expression of RUNX1 target genes, and impacts cell survival and differentiation. These inhibitors show efficacy against leukemia cells as well as basal-like (triple-negative) breast cancer cells. These inhibitors provide effective tools to probe the utility of targeting RUNX transcription factor function in other cancers.

Wind energy is known as one of the most efficient clean renewable energy sources and has attracted extensive research interests in both academic and industry fields. In this study, the effects of turbulent wind and voltage disturbance on a wind turbine drivetrain are analyzed, and a wind turbine drivetrain dynamic model combined with the electric model of a doubly fed induction generator is established. The proposed model is able to account for the dynamic interaction between turbulent wind, voltage disturbance, and mechanical system. Also, the effects of time-varying meshing stiffness, transmission error, and bearing stiffness are included in the mechanical part of the coupled dynamic model. From the resultant model, system modes are computed. In addition, by considering the actual control strategies in the simulation process, the effects of turbulent wind and voltage disturbance on the geared rotor system are analyzed. The computational results show that the turbulent wind and voltage disturbance can cause adverse effects on the wind turbine drivetrain, especially the gearbox. A series of parametric studies are also performed to understand the influences of generator and gearbox parameters on the drivetrain system dynamics. Finally, the appropriate generator parameters having a positive effect on the gearbox in alleviating the extreme loads and the modeling approach for investigating the transient performance of generator are discussed.

Purging plug refractories in China typically contain around 3 mass % of super-fine chromium oxide in the matrix in order to improve the performance of the purging plugs, primarily, slag corrosion and wear resistance. Alternatives to chromium oxide containing refractories have gained interest due to health concerns related to the formation of soluble chromium compounds over long storage periods of refractory wastes. Super-ground reactive alumina can replace chromium oxide in purging plug refractories and this paper discussed the new reactive alumina E-SY 88 in comparison to chromium oxide in a typical purging plug castable. The mixing behaviour, wet castable properties, as well as cured, dried, and fired properties at different temperatures up to 1 600 °C were compared. In addition, the hot modulus of rupture, creep behaviour, thermal shock resistance and slag corrosion resistance were tested. The microstructure after slag corrosion was investigated by SEM. The results prove that E-SY 88 is an economically viable technical alternative to chromium oxide in purging plug refractories. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the primary cause of death in cancer cases, with significant public health concern worldwide. Despite the overall decline in the incidence and mortality rates of HCC in recent years in recent years, the emergence of metabolic liver disease-related HCC is causing heightened concern, especially in countries like the United States, the United Kingdom, and P.R. China. The escalation of metabolic liver disease-related HCC is attributed to a combination of factors, including genetic predisposition, lifestyle choices, and changes in the living environment. However, the pathogenesis of metabolic liver disease-associated HCC remains imperfect. In this review, we encapsulate the latest advances and essential aspects of the pathogenesis of metabolic liver disease-associated HCC, including alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and inherited metabolic liver diseases. [ABSTRACT FROM AUTHOR]