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.

Harnessing the power of Calculus bovis:Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma

In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis.CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6,mitogen-activated protein kinase 8,vascular endothelial growth factor,and caspase-3,offering anti-inflammatory and hepatoprotective benefits.The manuscript also discusses CB sativus(CBS),an artificial substitute,which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models.We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota,and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.

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.

Exploring a new chapter in traditional Chinese medicine:The potential of Calculus bovis in liver cancer treatment

In the ongoing quest for new treatments in medicine,traditional Chinese medicine offers unique insights and potential.Recently,studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage polarisation by modulating the Wnt/β-catenin signalling pathway to suppress liver cancer have undoubtedly revealed new benefits and hope for this field of research.The purpose of this article is to comment on this study and explore its strengths and weaknesses,thereby providing ideas for the future treatment of liver cancer.

Assessment of the methods for determining net radiation at different time-scales of meteorological variables

When modeling the soil/atmosphere interaction,it is of paramount importance to determine the net radiation flux.There are two common calculation methods for this purpose.Method 1 relies on use of air temperature,while Method 2 relies on use of both air and soil temperatures.Nowadays,there has been no consensus on the application of these two methods.In this study,the half-hourly data of solar radiation recorded at an experimental embankment are used to calculate the net radiation and long-wave radiation at different time-scales(half-hourly,hourly,and daily) using the two methods.The results show that,compared with Method 2 which has been widely adopted in agronomical,geotechnical and geo-environmental applications.Method 1 is more feasible for its simplicity and accuracy at shorter time-scale.Moreover,in case of longer time-scale,daily for instance,less variations of net radiation and long-wave radiation are obtained,suggesting that no detailed soil temperature variations can be obtained.In other words,shorter time-scales are preferred in determining net radiation flux.

MEASUREMENT-BASED ADMISSION CONTROL USING MULTIPLE TIME-SCALES TEST

A new measurement-based admission control algorithm to support Quality of Service(QoS) demand is proposed for soft real-time applications. In the algorithm, admission test is performed across Multiple Time-Scales (MTS) to accurately capture traffic fluctuation on various time-scales. By applying the QoS requirements directly to admission test, the MTS algorithm can properly meet the QoS target and maximize the bandwidth utilization.

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.

Fast X-ray imaging beamline at SSRF

The fast X-ray imaging beamline(BL16U2)at Shanghai Synchrotron Radiation Facility(SSRF)is a new beamline that provides X-ray micro-imaging capabilities across a wide range of time scales,spanning from 100 ps toμs and ms.This beamline has been specifically designed to facilitate the investigation of a wide range of rapid phenomena,such as the deformation and failure of materials subjected to intense dynamic loads.In addition,it enables the study of high-pressure and high-speed fuel spray processes in automotive engines.The light source of this beamline is a cryogenic permanent magnet undulator(CPMU)that is cooled by liquid nitrogen.This CPMU can generate X-ray photons within an energy range of 8.7-30 keV.The beamline offers two modes of operation:monochromatic beam mode with a liquid nitrogen-cooled double-crystal monochromator(DCM)and pink beam mode with the first crystal of the DCM out of the beam path.Four X-ray imaging methods were implemented in BL16U2:single-pulse ultrafast X-ray imaging,microsecond-resolved X-ray dynamic imaging,millisecond-resolved X-ray dynamic micro-CT,and high-resolution quantitative micro-CT.Furthermore,BL16U2 is equipped with various in situ impact loading systems,such as a split Hopkinson bar system,light gas gun,and fuel spray chamber.Following the completion of the final commissioning in 2021 and subsequent trial operations in 2022,the beamline has been officially available to users from 2023.

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.