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.

GLOBAL SOLUTIONS IN THE CRITICAL SOBOLEV SPACE FOR THE LANDAU EQUATION

The Landau equation is studied for hard potential with-2≤γ≤1.Under a perturbation setting,a unique global solution of the Cauchy problem to the Landau equation is established in a critical Sobolev space H_(x)^(d)L_(v)^(2)(d>3/2),which extends the results of[11]in the torus domain to the whole space R_(x)^(3).Here we utilize the pseudo-differential calculus to derive our desired result.

THE GLOBAL EXISTENCE OF STRONG SOLUTIONS FOR A NON-ISOTHERMAL IDEAL GAS SYSTEM

We investigate the global existence of strong solutions to a non-isothermal ideal gas model derived from an energy variational approach.We first show the global wellposedness in the Sobolev space H^(2)(R^(3)) for solutions near equilibrium through iterated energy-type bounds and a continuity argument.We then prove the global well-posedness in the critical Besov space B^(3/2)_(2,1) by showing that the linearized operator is a contraction mapping under the right circumstances.

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.

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.

Using laparoscope to remove an ectopic intrauterine device in the anterior wall of urinary bladder:A case report

BACKGROUND An intrauterine device(IUD)is a contraceptive device placed in the uterine cavity and is a common contraceptive method for Chinese women.However,an IUD may cause complications due to placement time,intrauterine pressure and other factors.Ectopic IUDs are among the most serious complications.Ectopic IUDs are common in the myometrium and periuterine organs,and there are few reports of ectopic IUDs in the urinary bladder,especially in the anterior wall.CASE SUMMARY A 52-year-old woman was hospitalized due to a urinary bladder foreign body found via abdominal ultrasound and computed tomography(CT)examination.The patient had a 2-year history of recurrent abdominal distension and lower abdominal pain,accompanied by frequent urination,urgency,dysuria and other discomfort.Ultrasound examination revealed foreign bodies in the bladder cavity,with calculus on the surface of the foreign bodies.CT revealed a circular foreign body on the anterior wall of the urinary bladder,suggesting the possibility of an ectopic IUD.After laparoscopic exploration,an annular IUD was found in the anterior wall of urinary bladder,and an oval calculus with a diameter of approximately 2 cm was attached to the surface of the bladder cavity.The IUD and calculus were successfully and completely removed.The patient recovered well after surgery.CONCLUSION Abdominal ultrasound and CT are effective methods for detecting ectopic IUDs.The IUD is located in the urinary bladder and requires early surgical treatment.The choice of surgical method is determined by comprehensively considering the depth of the IUD in the bladder muscle layer,the situation of complicated calculus,the situation of intravesical inflammation and medical technology and equipment.

Unveiling the anticancer effect of traditional Chinese herbal medicine

In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.

Fault Diagnosis Method of Rolling Bearing Based on ESGMD-CC and AFSA-ELM

Incomplete fault signal characteristics and ease of noise contamination are issues with the current rolling bearing early fault diagnostic methods,making it challenging to ensure the fault diagnosis accuracy and reliability.A novel approach integrating enhanced Symplectic geometry mode decomposition with cosine difference limitation and calculus operator(ESGMD-CC)and artificial fish swarm algorithm(AFSA)optimized extreme learning machine(ELM)is proposed in this paper to enhance the extraction capability of fault features and thus improve the accuracy of fault diagnosis.Firstly,SGMD decomposes the raw vibration signal into multiple Symplectic geometry components(SGCs).Secondly,the iterations are reset by the cosine difference limitation to effectively separate the redundant components from the representative components.Additionally,the calculus operator is performed to strengthen weak fault features and make them easier to extract,and the singular value decomposition(SVD)weighted by power spectrum entropy(PSE)can be utilized as the sample feature representation.Finally,AFSA iteratively optimized ELM is adopted as the optimized classifier for fault identification.The superior performance of the proposed method has been validated by various experiments.

Review on Service Curves of Typical Scheduling Algorithms

In recent years,various internet architectures,such as Integrated Services(IntServ),Differentiated Services(DiffServ),Time Sensitive Networking(TSN)and Deterministic Networking(DetNet),have been proposed to meet the quality-of-service(QoS)requirements of different network services.Concurrently,network calculus has found widespread application in network modeling and QoS analysis.Network calculus abstracts the details of how nodes or networks process data packets using the concept of service curves.This paper summarizes the service curves for typical scheduling algorithms,including Strict Priority(SP),Round Robin(RR),Cycling Queuing and Forwarding(CQF),Time Aware Shaper(TAS),Credit Based Shaper(CBS),and Asynchronous Traffic Shaper(ATS).It introduces the theory of network calculus and then provides an overview of various scheduling algorithms and their associated service curves.The delay bound analysis for different scheduling algorithms in specific scenarios is also conducted for more insights.

A Dark Energy Hypothesis I

The cosmological constant, Λ, represents dark energy. The dark energy hypothesis (DEH) replaces Λ with a variable quantity, the cosmological parameter: Λ=1a2η2In this formula, “a” is the scale factor and η the conformal time: adη = cdt. A companion paper (DEH II) develops and explores a cosmological model with this variable parameter. This paper portrays the origin of the cosmological parameter in the uncoupling of time and space in the early universe from a prior state in which the comoving coordinates x0 = η and x1 = χ, the cosmic latitude, are coupled. In this hypothesis dark matter is a co-product of the decoupling, but its nature remains mysterious.

Ln^(3+)在LnF_3-LiCl-KCl熔盐体系中的电化学行为

钍的分离和再利用是熔盐堆钍铀燃料循环的重要组成部分,钍与裂变产物特别是化学性质相似的镧系元素的分离是熔盐堆氟盐燃料处理的关键之一。利用循环伏安法和方波伏安法研究了773 K下多种镧系元素氟化物(w=3%)在LnF_3-LiCl-KCl熔盐中的电化学行为。研究结果表明:Ce^(3+)和Gd^(3+)在惰性电极上均一步还原为金属,Nd^(3+)则是通过两步反应还原为金属,而Sm^(3+)和Eu^(3+)只能还原为低价态的Sm^(2+)和Eu^(2+);Th和Ln在惰性金属阴极上的析出电位差ΔE均大于0.19 V,在LiCl-KCl熔盐体系中实现Th与Ln的电化学分离在理论上是可行的;与纯氯盐体系相比,少量F-的引入不会改变Ln^(3+)在惰性电极上的电极反应过程,F-的存在使得Ln^(3+)在LiCl-KCl熔盐中的活度降低,从而导致扩散系数减小。此研究结果为了解Th4+)和Ln^(3+)在含F-氯盐体系中的电化学行为和建立可行的分离方法提供了基础实验依据。

Variational Approach to Heat Conduction Modeling

It is known that Fourier’s heat equation, which is parabolic, implies an infinite velocity propagation, or, in other words, that the mechanism of heat conduction is established instantaneously under all conditions. This is unacceptable on physical grounds in spite of the fact that Fourier’s law agrees well with experiment. However, discrepancies are likely to occur when extremely short distances or extremely short time intervals are considered, as they must in some modern problems of aero-thermodynamics. Cattaneo and independently Vernotte proved that such process can be described by Heaviside’s telegraph equation. This paper shows that this fact can be derived using calculus of variations, by application of the Euler-Lagrange equation. So, we proved that the equation of heat conduction with finite velocity propagation of the thermal disturbance can be obtained as a solution to one variational problem.

The Absence of “Perfect Induction”in the Science

The present paper is finalized to show that the Science, even if considered in its two different Phenomenological Approaches at present known, is unable to assert that: “Thinks are like that”. This is because both the two Scientific Approaches previously mentioned have not the property of “the perfect induction”. Consequently, although they can even reach an experimental confirmation of the theoretical results, and thus a “valid description” of the various phenomena of the surrounding world, such a description has not an “absolute value”. In fact, it always and only has an “operative validity”, that is, it exclusively and solely refers to an “experimental point of view”. This means that such an “operative validity” cannot represent the basis for a logical process characterized by a “perfect induction”. In addition, the Traditional Scientific Approach is also characterized by “Insoluble” Problems, “Intractable Problems”, Problems with “drifts”, which could generally be termed as “side effects”. On the other hand, the same com-possible Scientific Approach based on the Emerging Quality of Self-Organizing Systems, also presents its “Emerging Exits”. Consequently, none of the two mentioned scientific Approaches has the “gift” of “the perfect induction”. However, there are significant differences between the two. Differences that may “suggest” the most appropriate choice among them for an “operative point of view”. This conclusion will be com-proved by considering, with particular reference, both the “side effects”, which are related to the Traditional Approach and, on the other hand, the “Emerging Exits”, which specifically pertain to the new Scientific Approach based on the Emerging Quality of Self-Organizing Systems.

Elements of Electromagnetic Matter

Originally, Maxwell attempted to express his electromagnetic theory using four-dimensional mathematics of quaternions. Maxwell’s equations were later re-written in a three-dimensional real vector form, which is how the theory is presented today. Thus, an interesting question remains whether we can derive electromagnetic equations analytically from the basic mathematical principles of quaternion algebra and calculus, resulting in general and analytic matter equations. This question seems highly intriguing. Previously, we developed a mathematical theory of time using a normed division algebra of real quaternions [1]. In this study, we extend the theory of time by presenting a new analytical derivation of electromagnetic matter equations using the calculus of real quaternions, as originally intended by Maxwell. Therefore, we propose a novel mathematical definition of the quaternion path derivative using the properties of quaternion division. We then apply the quaternion derivative to an external electromagnetic potential and assume that the first quaternion derivative represents the quaternion electromagnetic force. Next, we assume that the second derivative, or quaternion Laplacian operator, applied to an external electromagnetic potential leads to the quaternion electromagnetic current density. The new analytical expressions are similar to the original empirical Maxwell equations, except for an additional scalar electric field, which allows for a novel formulation of Ohm’s conductivity law. We demonstrate that the resulting analytical equations can be written equivalently using either electromagnetic potentials or fields. Finally, we summarize the key postulates and equations of the new electromagnetic matter theory, which were based on normed division algebra and the calculus of quaternions. The resulting theory appears to be a useful analytical enhancement of the original Maxwell equations, and therefore, seems highly comprehensive, logical, and compelling.