Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

Promise and challenges of traditional Chinese medicine,specifically Calculus bovis,in liver cancer treatment

Liver cancer,one of the most common malignancies worldwide,ranks sixth in incidence and third in mortality.Liver cancer treatment options are diverse,inclu-ding surgical resection,liver transplantation,percutaneous ablation,transarterial chemoembolization,radiotherapy,chemotherapy,targeted therapy,immuno-therapy,and traditional Chinese medicine(TCM).A multidisciplinary team(MDT)is essential to customize treatment plans based on tumor staging,liver function,and performance status(PS),ensuring individualized patient care.Treatment decisions require a MDT to tailor strategies based on tumor staging,liver function,and PS,ensuring personalized care.The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer,improving overall prognosis.However,many patients do not respond effectively to these treatments and ultimately succumb to the disease.Modern oncology treatments,while extending patient survival,often come with severe side effects,resistance,and damage to the body,negatively impacting quality of life.Huang et al's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis,enhancing our understanding of TCM and contributing to new liver cancer treatment strategies.For over 5000 years,TCM has been used in East Asian countries like China to treat various diseases,including liver conditions.Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments,integrated TCM therapies could provide significant breakthroughs.

Calculus bovis in hepatocellular carcinoma:Tumor molecular basis,Wnt/β-catenin pathway role,and protective mechanism

In this editorial,we comment on the recent article by Huang et al.The editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma(HCC),mechanism of Wnt/β-catenin pathway in HCC,and protective mechanism of Calculus bovis(CB)in HCC.Liver cancer is the fourth most common cause of cancer-related deaths globally.The most prevalent kind of primary liver cancer,HCC,is typically brought on by long-term viral infections(hepatitis B and C),non-alcoholic steatohepatitis,excessive alcohol consumption,and other conditions that can cause the liver to become chronically inflamed and cirrhotic.CB is a wellknown traditional remedy in China and Japan and has been used extensively to treat a variety of diseases,such as high fever,convulsions,and stroke.Disturbances in lipid metabolism,cholesterol metabolism,bile acid metabolism,alcohol metabolism,and xenobiotic detoxification lead to fatty liver disease and liver cirrhosis.Succinate,which is a tricarboxylic acid cycle intermediate,is vital to energy production and mitochondrial metabolism.It is also thought to be a signaling molecule in metabolism and in the development and spread of liver malignancies.The Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic development.Cancer is frequently caused by the dysregulation of the Wnt/β-catenin signaling pathway.In HCC liver carcinogenesis,Wnt/β-catenin signaling is activated by the expression of downstream target genes.Communication between the liver and the gut exists via the portal vein,biliary tract,and systemic circulation.This"gutliver axis"controls intestinal physiology.One of the main factors contributing to the development,progression,and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling pathway.Therefore,understanding this pathway is essential to treating HCC.Eleven ingredients of CB,particularly oleanolic acid,ergosterol,and ursolic acid,have anti-primary liver cancer properties.Additionally,CB is important in the treatment of primary liver cancer through pathways linked to immune system function and apoptosis.CB also inhibits the proliferation of cancer stem cells and tumor cells and controls the tumor microenvironment.In the future,clinicians may be able to recommend one of many potential new drugs from CB ingredients to treat HCC expression,development,and progress.

Anti-tumor efficacy of Calculus bovis: Suppressing liver cancer by targeting tumor-associated macrophages

Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.

From traditional Chinese medicine formulations to effective anticancer agents:Insights from Calculus bovis

This editorial examines the therapeutic potential of traditional Chinese medicine(TCM)for aggressive cancers,particularly liver cancer.It highlights the study by Huang et al,which shows how Calculus bovis,a component of the TCM Pien Tze Huang,suppresses liver cancer by inhibiting M2 macrophage polarization via the Wnt/β-catenin pathway.This research emphasizes the importance of transitioning from effective TCM formulations to isolating active components and understanding their mechanisms.While the study provides valuable insights,it primarily focuses on the Wnt/β-catenin pathway and does not delve deeply into the mechanisms of individual components.Future research should aim to comprehensively study these components,explore their interactions,and validate findings through clinical trials.This approach will integrate traditional wisdom with modern scientific validation,advancing the development of innovative cancer treatments based on TCM formulations.

Pixel’s Quantum Image Enhancement Using Quantum Calculus

The current study provides a quantum calculus-based medical image enhancement technique that dynamically chooses the spatial distribution of image pixel intensity values.The technique focuses on boosting the edges and texture of an image while leaving the smooth areas alone.The brain Magnetic Resonance Imaging(MRI)scans are used to visualize the tumors that have spread throughout the brain in order to gain a better understanding of the stage of brain cancer.Accurately detecting brain cancer is a complex challenge that the medical system faces when diagnosing the disease.To solve this issue,this research offers a quantum calculus-based MRI image enhancement as a pre-processing step for brain cancer diagnosis.The proposed image enhancement approach improves images with low gray level changes by estimating the pixel’s quantum probability.The suggested image enhancement technique is demonstrated to be robust and resistant to major quality changes on a variety ofMRIscan datasets of variable quality.ForMRI scans,the BRISQUE“blind/referenceless image spatial quality evaluator”and the NIQE“natural image quality evaluator”measures were 39.38 and 3.58,respectively.The proposed image enhancement model,according to the data,produces the best image quality ratings,and it may be able to aid medical experts in the diagnosis process.The experimental results were achieved using a publicly available collection of MRI scans.

A Vector Tensor Calculus Description of a Euclidean Space

We present a tensor description of Euclidean spaces that emphasizes the use of geometric vectors which leads to greater geometric insight and a higher degree of organization in analytical expressions. We demonstrate the effectiveness of the approach by proving a number of integral identities with vector integrands. The presented approach may be aptly described as absolute vector calculus or as vector tensor calculus.

F-fuzzy Calculus System

A formalized calculus system called F_fuzzy calculus system, which is a symbol deduction system to formalize fuzzy inference, is constructed in this paper. The fuzzy modus ponens was completely formalized in this calculus system.

一本有新意的微积分教材——评美国MIT教授Strang新编《CALCULUS》

微积分教材数以千计,每年都有不少新作问世,但有新意者却如凤毛麟角。91年夏我到美国参加第二届国际工业与应用数学大会(ICIAM’91),在大会展厅看到美国麻省理工学院(MIT)数学系教授、美国工业与应用数学学会(SIAM)教育委员会主席Strang教授刚刚出版的《CALCULUS》,很有特色,会后应邀访问MIT。

One Sound and Complete <i>R</i>-Calculus with Pseudo-Subtheory Minimal Change Property

The AGM axiom system is for the belief revision (revision by a single belief), and the DP axiom system is for the iterated revision (revision by a finite sequence of beliefs). Li [1] gave an R-calculus for R-configurations &Delta;|&Gamma;,?where?&Delta;?is a set of atomic formulas or the negations of atomic formulas, and?&Gamma;?is a finite set of formulas. In propositional logic programs, one R-calculus N will be given in this paper, such that N is sound and complete with respect to operator s(&Delta;,t), where s(&Delta;,t)is a pseudo-theory minimal change of t by?&Delta;.

基于Pi-Calculus的跨组织工作流建模方法

针对跨组织协同环境下的业务流程建模技术的不足,提出了一个新的用于跨组织业务流程的形式化建模方法。首先根据工作流管理联盟(W fMC)的有关工作流过程定义接口规范,利用Pi-Calculus技术对跨组织业务流程结构进行了形式化定义。此外,利用Pi-Calculus特有机制对并发流程及其之间的通信进行描述。提出的方法可以有效用于不同业务流程间的协同工作,并且适合于对分布式协同环境下的工作流进行建模。

Effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in rabbits with schistosomiasis

AIM:To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation(ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS:The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco.The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy.The expression of fibronectin(FN) and laminin(LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS:Under light microscope,the alveolar exudation in the lung tissue was more frequently observed in the control group,while the alveolar space was fairly dry in the lung tissue of ICCBco group.Under electron microscope,more alveolar exudation in the lung tissue,and moremacrophages,alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group.In ICCBco group,fibers within the alveolar interspace slightly increased in some lung regions,and the structure of typeⅠepithelium,basement membrane and endodermis was complete,and no obvious exudation from the alveolar space,and novascular congestion could be observed.There was a positive or strong positive expression of FN and LN in the lung tissue of the control group,while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION:ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.

Transfer function modeling and analysis of the open-loop Buck converter using the fractional calculus

Based on the fact that the real inductor and the real capacitor are fractional order in nature and the fractional calculus,the transfer function modeling and analysis of the open-loop Buck converter in a continuous conduction mode（CCM） operation are carried out in this paper.The fractional order small signal model and the corresponding equivalent circuit of the open-loop Buck converter in a CCM operation are presented.The transfer functions from the input voltage to the output voltage,from the input voltage to the inductor current,from the duty cycle to the output voltage,from the duty cycle to the inductor current,and the output impedance of the open-loop Buck converter in CCM operation are derived,and their bode diagrams and step responses are calculated,respectively.It is found that all the derived fractional order transfer functions of the system are influenced by the fractional orders of the inductor and the capacitor.Finally,the realization of the fractional order inductor and the fractional order capacitor is designed,and the corresponding PSIM circuit simulation results of the open-loop Buck converter in CCM operation are given to confirm the correctness of the derivations and the theoretical analysis.

Performance Evaluation for SDN Deployment: an Approach Based on Stochastic Network Calculus

The Open Flow implementations(SDNs) have been deployed increasingly on varieties of networks in research institutions as well as commercial institutions. To develop an Open Flow implementation, it is required to understand the performance of the network. A few benchmark tools(e.g., Cbench and OFlops) can be used to measure the network performance, while these tools take considerable time to simulate traffic behaviors and generate the required results,therefore extending the development time. In this paper, we present an analytical model, which is based on stochastic network calculus theory, for evaluating the performance of switch to controller.The previous studies show that stochastic network calculus can provide realistic emulation of real network traffic behaviors. Our model is evaluated by using both simulation tool and realistic testbed.The results show the stochastic network calculus based analysis model can realistically measure the network performance of the end-to-end properties between controller and switch.

Modelling long-term deformation of granular soils incorporating the concept of fractional calculus

Many constitutive models exist to characterise the cyclic behaviour of granular soils but can only simulate deformations for very limited cycles. Fractional derivatives have been regarded as one potential instrument for modelling memory-dependent phenomena. In this paper, the physical connection between the fractional derivative order and the fractal dimension of granular soils is investigated in detail. Then a modified elasto-plastic constitutive model is proposed for evaluating the long-term deformation of granular soils under cyclic loading by incorporating the concept of fac- tional calculus. To describe the flow direction of granular soils under cyclic loading, a cyclic flow potential consider- ing particle breakage is used. Test results of several types of granular soils are used to validate the model performance.

CONNECTION BETWEEN THE ORDER OF FRACTIONAL CALCULUS AND FRACTIONAL DIMENSIONS OF A TYPE OF FRACTAL FUNCTIONS

The linear relationship between fractal dimensions of a type of generalized Weierstrass functions and the order of their fractional calculus has been proved. The graphs and numerical results given here further indicate the corresponding relationship.

ON THE FRACTIONAL CALCULUS FUNCTIONS OF A FRACTAL FUNCTION

Based on the combination of fractional calculus with fractal functions, a new type of functions is introduced; the definition, graph, property and dimension of this function are discussed.

Approach for workflow modeling using π-calculus

As a variant of process algebra, π calculus can describe the interactions between evolving processes. By modeling activity as a process interacting with other processes through ports, this paper presents a new approach: representing workflow models using π calculus. As a result, the model can characterize the dynamic behaviors of the workflow process in terms of the LTS (Labeled Transition Semantics) semantics of π calculus. The main advantage of the workflow model's formal semantic is that it allows for verification of the model's properties, such as deadlock free and normal termination. Moreover, the equivalence of workflow models can be checked through weak bisimulation theorem in the π calculus, thus facilitating the optimization of business processes.

Variational Calculus With Conformable Fractional Derivatives

Invariant conditions for conformable fractional problems of the calculus of variations under the presence of external forces in the dynamics are studied. Depending on the type of transformations considered, different necessary conditions of invariance are obtained. As particular cases, we prove fractional versions of Noether's symmetry theorem. Invariant conditions for fractional optimal control problems, using the Hamiltonian formalism, are also investigated. As an example of potential application in Physics, we show that with conformable derivatives it is possible to formulate an Action Principle for particles under frictional forces that is far simpler than the one obtained with classical fractional derivatives.

Network Calculus在机载雷达设计中的应用

Network Calculus是一种基于最小加代数理论来分析网络数据流的方法,它已被广泛应用于工业、航空和航天的复杂网络设计中。机载雷达要求系统具有高实时性,尤其对嵌入式任务的调度有严格的时序要求。在机载雷达的设计中应用此理论,可以在系统前期设计时提供实时性的理论依据和保障,为雷达系统的实时性设计提供了一种方法和手段。