With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming mor...With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.展开更多
Onion plants form spherical bulbs under long-day conditions.Substances regulating bulb formation remain unknown.In the course of chemical studies on the bulb formation,α-linolenic acid was isolated from onion extract...Onion plants form spherical bulbs under long-day conditions.Substances regulating bulb formation remain unknown.In the course of chemical studies on the bulb formation,α-linolenic acid was isolated from onion extracts as an antibulbing substance,the amount of which was synchronized with the bulb formation.Since allene oxide synthase inhibitor canceled the antibulbing activity ofα-linolenic acid,it was disclosed that jasmonic acid concerns this regulation.Structure-activity-relationship study revealed that its(3R,7S)stereochemistry is necessary for showing its antibulbing activity.It is concluded that(3R,7S)-jasmonate derived fromα-linolenic acid actually participates in the regulation of bulb formation.展开更多
Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substa...Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.展开更多
This paper describes the investigation of the secretion of extracellular polymeric substances(EPS)by an extremely thermoacidophilic archaea,Metallosphaera sedula(M.sedula),during the bioleaching of pyrite under differ...This paper describes the investigation of the secretion of extracellular polymeric substances(EPS)by an extremely thermoacidophilic archaea,Metallosphaera sedula(M.sedula),during the bioleaching of pyrite under different temperatures and discusses the relationship among the EPS secretion,its heat resistance,and its ability to bioleach pyrite.The investigation results indicate that the amount of extracellular proteins is significantly higher than the amount of extracellular polysaccharides in the extracted EPS whether free cells or attached cells;these results are quite different from the behavior of mesophilic Acidithiobacillus ferrooxidans.Although the growth of M.sedula is inhibited at 80℃,the bioleaching ability of M.sedula is only slightly lower than that at the optimum growth temperature of 72℃ because of the heat resistance mechanism based on EPS secretion.The secretion of more extracellular proteins is an important heat resistance mechanism of M.sedula.展开更多
Drug overdose is the leading cause of death by injury in the United States.The incidence of substance use disorder(SUD)in the United States has increased steadily over the past two decades,becoming a major public heal...Drug overdose is the leading cause of death by injury in the United States.The incidence of substance use disorder(SUD)in the United States has increased steadily over the past two decades,becoming a major public health problem for the country.The drivers of the SUD epidemic in the United States have changed over time,characterized by an initial heroin outbreak between 1970 and 1999,followed by a painkiller outbreak,and finally by an ongoing synthetic opioid outbreak.The nature and sources of these abused substances reveal striking differences in the socioeconomic and behavioral factors that shape the drug epidemic.Moreover,the geospatial distribution of the SUD epidemic is not homogeneous.The United States has specific locations where vulnerable communities at high risk of SUD are concentrated,reaffirming the multifactorial socioeconomic nature of this epidemic.A better understanding of the SUD epidemic under a spatial epidemiology framework is necessary to determine the factors that have shaped its spread and how these patterns can be used to predict new outbreaks and create effective mitigation policies.This narrative minireview summarizes the current records of the spatial distribution of the SUD epidemic in the United States across different periods,revealing some spatiotemporal patterns that have preceded the occurrence of outbreaks.By analyzing the epidemic of SUD-related deaths,we also describe the epidemic behavior in areas with high incidence of cases.Finally,we describe public health interventions that can be effective for demographic groups,and we discuss future challenges in the study and control of the SUD epidemic in the country.展开更多
The fixation of leaves of Tanacetum vulgare L. in glutaraldehyde makes it possible to isolate chloroplasts without sacrificing an electron dense substance in the thylakoid lumen. The extraction of lipids from the chlo...The fixation of leaves of Tanacetum vulgare L. in glutaraldehyde makes it possible to isolate chloroplasts without sacrificing an electron dense substance in the thylakoid lumen. The extraction of lipids from the chloroplasts isolated from the leaves preliminarily fixed in glutaraldehyde has demonstrated that glycerolipids (galactolipids and phospholipids) are not manifested in TLC, whereas isoprenoid lipids (chlorophyll, carotenoids) are manifested. Presumably, isoprenoid lipids are not fixed with glutaraldehyde and are extracted from the thylakoid membrane. The ultrastructural control demonstrates that the electron dense substance from the thylakoid lumen is also extracted. It is possible that this substance is of isoprenoid nature.展开更多
Based on the idea of hypothetical 4-dimensial substance with an inverse population of energy levels, a model of accelerated expansion of the Universe has been developed, which describes Hubble diagrams with great accu...Based on the idea of hypothetical 4-dimensial substance with an inverse population of energy levels, a model of accelerated expansion of the Universe has been developed, which describes Hubble diagrams with great accuracy for type Ia supernovae, quasars and gamma-ray burst sources at the Hubble parameter value of 67.7 km/s/Mpc, coinciding with the value obtained from analysis of inhomogeneities of relic radiation. Calculations at the Hubble parameter value of 73.5 km/s/Mpc, obtained using the ΛCDM model based on the analysis of data on type Ia supernovae and cepheids, differ markedly from the observed data. An explanation of the two values of the Hubble constant is proposed. It is shown that in this model, the magnitude of 13.8 billion years characterizes not the age of the Universe, but the time of propagation of light from those galaxes whose acceleration of removal has a minimal value. Based on the recently discovered curvature of the Universe, estimates are given of the lower limits of its size and lifetime, which turned out to be at least 270 billon years. The probability of transition from the excited state to the underlying energy levels of a hypothetical 4-dimensial substance, as well as the low of increasing energy density as a result of transitions to the underlying levels of this substance, is determined.展开更多
Background:Substance abuse has become an increasingly serious socio-medical issue in recent decades.Human health is affected by the socio-cultural environment,which has a direct impact on his psychophysical developmen...Background:Substance abuse has become an increasingly serious socio-medical issue in recent decades.Human health is affected by the socio-cultural environment,which has a direct impact on his psychophysical development and well-being.However,sociocultural factors such as bad habits influence lifestyle and behavior,leading to significant health and social problems for substance abusers.Objective:The present study is to evaluate the phenomenology and socio-demographic characteristics of abusers and compare some of the characteristics randomly.The main objectives of this study are a.To evaluate the socio-demographic profile.b.To find out the pattern of substance use.c.To evaluate the association of phenomenology.d.To find out about substance-related disorders among the substance abuse patients.Materials and methods:There was an observational study conducted in the drug de-addiction unit at Taif,Eradah,and Mental Health Hospital in Saudi Arabia.This study included all substance abusers admitted to the hospital who met the inclusion and exclusion criteria.The study included patients of both genders admitted to the drug de-addiction unit between April 2021 and October 2022.Based on a descriptive statistical analysis,categorical variables were presented as frequencies and percentages.Results:An observational study was conducted for nearly one and a half years.We interviewed 358 substance abuse patients following a systematic sampling procedure in a peaceful,non-threatening environment.Among the 358 substance users,353(98.60%)were male and 5(1.39%)were female.According to the survey,117(32.68%)of the participants reported abusing substances during their 31-40 years of age,followed by 102(28.49%)during their 25-30 years of age.The predominant level of substance abuse was among the unemployed 163(45.53%),followed by students 105(29.33%).It was found that 58.66%of all respondents had initiated abuse between the ages of 18-24 years of age.Conclusion:In our study,combined substances like amphetamine and cannabis abusers were most prevalent because these are the most popular illicit drugs which are easily available.Islamic culture prohibits alcohol consumption both religiously and legally,making alcohol abuse the least prevalent of all drug addictions.展开更多
Although many studies have found that cadmium(Cd)can be toxic to microalgae,only a few reports focused on the role of extracellular polymeric substances(EPS)in Cd(Ⅱ)detoxification.The biochemical and physiological en...Although many studies have found that cadmium(Cd)can be toxic to microalgae,only a few reports focused on the role of extracellular polymeric substances(EPS)in Cd(Ⅱ)detoxification.The biochemical and physiological endpoints of Microcystis aeruginosa,including the composition and functional groups of soluble EPS(SL-EPS),loosely bound EPS(LB-EPS),and tightly bound EPS(TB-EPS),were detected to elucidate the toxicity and detoxification mechanisms of Cd(Ⅱ)for cyanobacteria.Toxicological and physiological assays on M.aeruginosa showed that the 0.25-mg/L Cd(Ⅱ)resulted in a larger inhibition on growth and F_(v)/F_(m).Nevertheless,Cd(Ⅱ)significantly induced much higher contents of superoxide dismutase(SOD),intracellular microcystin LR(MC-LR),extracellular MC-LR,and EPS.Scanning electron microscopy with energy dispersive X-ray spectroscopy confirmed that Cd(Ⅱ)was absorbed into the EPS layer.Fourier transform infrared spectrum analysis revealed that the functional groups bound with Cd(Ⅱ)of algae biomass,SL-EPS,LB-EPS,and TB-EPS were somewhat different.The C=O/C=N groups ofδ-lactam or protein were their prominent functional groups,suggesting that amide or proteins in the EPS played a key role in the adsorption in Cd(Ⅱ).The concentration of 0.25 mg/L of Cd(Ⅱ)may change the chemical structure of EPS by altering the production of protein-like substances containing tryptophan.This study indicated that M.aeruginosa could detoxify Cd(Ⅱ)stress via induction of antioxidant capacity(higher SOD activity and MC synthesis),EPS production,and modification in chemical structure of EPS.展开更多
This essay explores the connections between Hoarding Disorder and Substance Use Disorder,two distinct mental health conditions with clear diagnostic criteria in the DSM-5.Hoarding Disorder,marked by excessive possessi...This essay explores the connections between Hoarding Disorder and Substance Use Disorder,two distinct mental health conditions with clear diagnostic criteria in the DSM-5.Hoarding Disorder,marked by excessive possession accumulation and difficulties in letting go,affects 2-6%of the global population,leading to severe consequences.Potential causes include genetic predisposition,neural issues,and traumatic experience.Substance Use Disorder is influenced by more societal factors.Both disorders share a comorbidity in Attention-Deficit/Hyperactivity Disorder(ADHD).Network analysis shows a strong direct relationship between Hoarding Disorder and ADHD,while social influences increase ADHD prevalence in Substance Use Disorder individuals.Moreover,both disorders benefit from Cognitive Behavioral Therapy(CBT).Exposure and Ritual Prevention effectively address hoarding symptoms,while CBT for Substance Use Disorder focuses on the interplay between thoughts,emotions,and actions.Despite being classified as a mental illness in DSM-5,Hoarding Disorder receives less attention than Substance Use Disorder.This essay aims to raise awareness of Hoarding Disorder by highlighting its commonalities with Substance Use Disorder in terms of causes,comorbidities,and treatment approaches.展开更多
Soybean is one of the important crops in China. Soymilk, a traditional neutral plant-based protein drink, is rich in high quality proteins. Although soybean milk is rich in nutrients, its marketing among consumers, es...Soybean is one of the important crops in China. Soymilk, a traditional neutral plant-based protein drink, is rich in high quality proteins. Although soybean milk is rich in nutrients, its marketing among consumers, especially those in Western countries who are used to peaceful flavor, has been limited due to the adverse flavor impact brought by its special composition. In recent years, with the increasing attention to the nutritional value of soymilk, the flavor of soymilk has become a popular research object for scholars at home and abroad. The flavor components of soymilk are mainly volatile small molecular compounds produced by enzymatic reactions catalyzed by lipoxygenase(LOX). After formation, they interact with protein macromolecules to form the overall flavor of soymilk. At present, there are many methods to control the off-odor of soymilk at home and abroad, including physical heating methods, chemical methods, biological enzymatic digestion methods, mask methods, and a variety of breeding methods. These methods effectively reduce the off-odor of soymilk, but all of them have shortcomings. Currently, the sensory characteristics of the beany odor in soymilk are evaluated mainly by traditional human sensory scoring along with the assistance of modern instrument analysis of volatile flavor substances using headspace solid phase microextraction(SPME) gas chromatography coupled with-mass spectrometry(GC-MS). This paper summarized the research results of volatile flavor substances in soymilk in recent years and the sensory evaluation methods of soymilk at home and abroad, and looked forward to the future development direction, hoping to provide some theoretical bases and reference detection methods for solving the problem of soymilk flavor in the future.展开更多
Substance use disorders(SUDs)are a growing problem among older adults.Acamprosate,disulfiram,and naltrexone are United States Food and Drug Administration(referred to as FDA)approved for the treatment of alcohol use d...Substance use disorders(SUDs)are a growing problem among older adults.Acamprosate,disulfiram,and naltrexone are United States Food and Drug Administration(referred to as FDA)approved for the treatment of alcohol use disorder,and buprenorphine is approved for the treatment of opiate use disorder among adults.However,the data on the use of these medications for the treatment of SUDs among older adults are unclear from randomized controlled trials(referred to as RCTs).A review of the literature indicates that there are only two RCTs that evaluated the use of pharmacologic agents for SUDs among older adults(≥50 years).One trial evaluated the use of naltrexone when compared to placebo for the treatment of alcohol use disorder among individuals,50-70 years in age.The other trial evaluated the use of naltrexone or placebo as adjuncts with sertraline in the treatment of alcohol use disorder among individuals older than 55 years in age.Both trials indicated that the use of naltrexone reduced the rates of relapse among older adults with alcohol use disorder.However,we did not identify any RCTs that studied the use of buprenorphine,acamprosate,or disulfiram for SUDs among older adults.Based on available evidence,it would be safe to conclude that limited data indicate some efficacy for naltrexone in the treatment of alcohol use disorder among older adults.However,data from controlled trials on the use of other medications that are FDA approved for the treatment of SUDs among younger adults are nonexistent among older adults with SUDs.展开更多
Rhizobium tropici-derived extracellular polymeric substances (EPS) have been used in soils to enhance soil structures and mitigate soil erosions. However, information on their use to improve soil health and fertility ...Rhizobium tropici-derived extracellular polymeric substances (EPS) have been used in soils to enhance soil structures and mitigate soil erosions. However, information on their use to improve soil health and fertility indicators, and plant growth is limited. In a greenhouse study, we investigated their effects on some soil health, soil fertility indices, and the growth of black-eyed peas (Vigna unguiculate). Results showed that soils incubated with EPS significantly increased basal soil respiration, soil microbial biomass, permanganate oxidizable carbon (POC), and potentially mineralizable nitrogen (PMN). The EPS shifted microbial populations from bacteria to fungi and Gram (−ve) to Gram ( ve) bacteria. However, it had little or no effects on soil pH, soil organic matter (SOM), and cation exchange capacity (CEC). The EPS decreased soil moisture loss, increased soil aggregate stability, but delayed blacked-eyed peas germinations in the soils. At 0.1% (w/w) concentrations in soils, there was increase in plant root nodulations and vegetative growth. This study was carried out within 40 days of incubating soils with EPS or growing the black-eyed peas in a greenhouse study. The plant growth parameters were taken before flowering and fruiting. Further studies of the effects of incubating soils with the extracellular polymeric substances on plant growth. Soil microbial biomass, microbial diversities, and other soil fertility indices are deemed necessary.展开更多
Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of meta...Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of metaverse development,which is considered by many as the next-generation Internet.Specifically,Web3 technologies such as smart contracts and protocols like non-fungible tokens(NFTs)have supported the immersive and content-rich experience of current Web3 metaverse projects.展开更多
BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine u...BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocaine use.Methamphetamine-group subjects further showed a significantly lower score of conscientiousness,depressive,and psychiatric symptoms than subjects from the OSgroup.In both groups,a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment.CONCLUSION There are differences between methamphetamine users and users of other drugs,but not with regard to the effectiveness of treatment in this inpatient setting.There are differences in cognitive function and psychopathology between methamphetamine and other drugs users.The existing treatment options seem to be an effective approach in treating methamphetamine dependence.展开更多
The phenomenon of electrical attraction and repulsion between charged particles is well known, and described mathematically by Coulomb’s Law, yet until now there has been no explanation for why this occurs. There has...The phenomenon of electrical attraction and repulsion between charged particles is well known, and described mathematically by Coulomb’s Law, yet until now there has been no explanation for why this occurs. There has been no mechanistic explanation that reveals what causes the charged particles to accelerate, either towards or away from each other. This paper gives a detailed explanation of the phenomena of electrical attraction and repulsion based on my previous work that determined the exact wave-function solutions for both the Electron and the Positron. It is revealed that the effects are caused by wave interactions between the wave functions that result in Electromagnetic reflections of parts of the particle’s wave functions, causing a change in their momenta.展开更多
Present studies in physics assume that elementary particles are the building blocks of all matter, and that they are zero-dimensional objects which do not occupy space. The new I-Theory predicts that elementary partic...Present studies in physics assume that elementary particles are the building blocks of all matter, and that they are zero-dimensional objects which do not occupy space. The new I-Theory predicts that elementary particles do indeed have a substructure, three dimensions, and occupy space, being composed of fundamental particles called I-particles. In this article we identify the substructural pattern of elementary particles and define the quanta of energy that form each elementary particle. We demonstrate that the substructure comprises two classes of quanta which we call “attraction quanta” and “repulsion quanta”. We create a model that defines the rest-mass energy of each elementary particle and can predict new particles. Lastly, in order to incorporate this knowledge into the contemporary models of science, a revised periodic table is proposed.展开更多
The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric an...The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.展开更多
For phosphorus (P) recovery from wastewater, the effect of humic substances (HS) on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with syn...For phosphorus (P) recovery from wastewater, the effect of humic substances (HS) on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate (as P) and 20 mg/L HS (as dissolved organic carbon, DOC) at a constant pH value in the range of 8.0-10.0. The concentration variations of phosphate, calcium (Ca) and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction (XRD) and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH ≥9.0, the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations ≤3.5 mg/L, and at pH ≥ 9.0 and HS concentrations ≤ 10 mg/L, the final precipitates were proved to be hydroxyapatite (HAP) by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate.展开更多
Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs ...Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.展开更多
基金Jiangsu Province Higher Education Teaching Reform Research Key Project“Research and Reform of Industry-Needed Pharmacy Engineering Talents Incubation Mode from the Perspective of Industry-Teaching Integration and Innovation Drive”(2023JSJG077)。
文摘With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.
基金Supported by the Naito FoundationGrant-in-Aid for Scientific Research (22K05448)from Japan Society for the Promotion of Science.
文摘Onion plants form spherical bulbs under long-day conditions.Substances regulating bulb formation remain unknown.In the course of chemical studies on the bulb formation,α-linolenic acid was isolated from onion extracts as an antibulbing substance,the amount of which was synchronized with the bulb formation.Since allene oxide synthase inhibitor canceled the antibulbing activity ofα-linolenic acid,it was disclosed that jasmonic acid concerns this regulation.Structure-activity-relationship study revealed that its(3R,7S)stereochemistry is necessary for showing its antibulbing activity.It is concluded that(3R,7S)-jasmonate derived fromα-linolenic acid actually participates in the regulation of bulb formation.
基金financially supported by Natural Science Foundation of Shandong Province(No.ZR2023QH037)Medical and Health Science and Technology Development Program of Shandong Province(No.202203010622)+1 种基金GuangDong Basic and Applied Basic Research Foundation(No.2020A1515111005)China Postdoctoral Science Foundation(No.2018M643053).
文摘Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.
基金financially supported by the National Natural Science Foundation of China (Nos. 31470230, 51320105006, 51604308, and 31100173)the Youth Talent Foundation of Hunan Province of China (No. 2017RS3003)the National Science Foundation of Hunan Province of China (No. 2018JJ2486)
文摘This paper describes the investigation of the secretion of extracellular polymeric substances(EPS)by an extremely thermoacidophilic archaea,Metallosphaera sedula(M.sedula),during the bioleaching of pyrite under different temperatures and discusses the relationship among the EPS secretion,its heat resistance,and its ability to bioleach pyrite.The investigation results indicate that the amount of extracellular proteins is significantly higher than the amount of extracellular polysaccharides in the extracted EPS whether free cells or attached cells;these results are quite different from the behavior of mesophilic Acidithiobacillus ferrooxidans.Although the growth of M.sedula is inhibited at 80℃,the bioleaching ability of M.sedula is only slightly lower than that at the optimum growth temperature of 72℃ because of the heat resistance mechanism based on EPS secretion.The secretion of more extracellular proteins is an important heat resistance mechanism of M.sedula.
文摘Drug overdose is the leading cause of death by injury in the United States.The incidence of substance use disorder(SUD)in the United States has increased steadily over the past two decades,becoming a major public health problem for the country.The drivers of the SUD epidemic in the United States have changed over time,characterized by an initial heroin outbreak between 1970 and 1999,followed by a painkiller outbreak,and finally by an ongoing synthetic opioid outbreak.The nature and sources of these abused substances reveal striking differences in the socioeconomic and behavioral factors that shape the drug epidemic.Moreover,the geospatial distribution of the SUD epidemic is not homogeneous.The United States has specific locations where vulnerable communities at high risk of SUD are concentrated,reaffirming the multifactorial socioeconomic nature of this epidemic.A better understanding of the SUD epidemic under a spatial epidemiology framework is necessary to determine the factors that have shaped its spread and how these patterns can be used to predict new outbreaks and create effective mitigation policies.This narrative minireview summarizes the current records of the spatial distribution of the SUD epidemic in the United States across different periods,revealing some spatiotemporal patterns that have preceded the occurrence of outbreaks.By analyzing the epidemic of SUD-related deaths,we also describe the epidemic behavior in areas with high incidence of cases.Finally,we describe public health interventions that can be effective for demographic groups,and we discuss future challenges in the study and control of the SUD epidemic in the country.
文摘The fixation of leaves of Tanacetum vulgare L. in glutaraldehyde makes it possible to isolate chloroplasts without sacrificing an electron dense substance in the thylakoid lumen. The extraction of lipids from the chloroplasts isolated from the leaves preliminarily fixed in glutaraldehyde has demonstrated that glycerolipids (galactolipids and phospholipids) are not manifested in TLC, whereas isoprenoid lipids (chlorophyll, carotenoids) are manifested. Presumably, isoprenoid lipids are not fixed with glutaraldehyde and are extracted from the thylakoid membrane. The ultrastructural control demonstrates that the electron dense substance from the thylakoid lumen is also extracted. It is possible that this substance is of isoprenoid nature.
文摘Based on the idea of hypothetical 4-dimensial substance with an inverse population of energy levels, a model of accelerated expansion of the Universe has been developed, which describes Hubble diagrams with great accuracy for type Ia supernovae, quasars and gamma-ray burst sources at the Hubble parameter value of 67.7 km/s/Mpc, coinciding with the value obtained from analysis of inhomogeneities of relic radiation. Calculations at the Hubble parameter value of 73.5 km/s/Mpc, obtained using the ΛCDM model based on the analysis of data on type Ia supernovae and cepheids, differ markedly from the observed data. An explanation of the two values of the Hubble constant is proposed. It is shown that in this model, the magnitude of 13.8 billion years characterizes not the age of the Universe, but the time of propagation of light from those galaxes whose acceleration of removal has a minimal value. Based on the recently discovered curvature of the Universe, estimates are given of the lower limits of its size and lifetime, which turned out to be at least 270 billon years. The probability of transition from the excited state to the underlying energy levels of a hypothetical 4-dimensial substance, as well as the low of increasing energy density as a result of transitions to the underlying levels of this substance, is determined.
文摘Background:Substance abuse has become an increasingly serious socio-medical issue in recent decades.Human health is affected by the socio-cultural environment,which has a direct impact on his psychophysical development and well-being.However,sociocultural factors such as bad habits influence lifestyle and behavior,leading to significant health and social problems for substance abusers.Objective:The present study is to evaluate the phenomenology and socio-demographic characteristics of abusers and compare some of the characteristics randomly.The main objectives of this study are a.To evaluate the socio-demographic profile.b.To find out the pattern of substance use.c.To evaluate the association of phenomenology.d.To find out about substance-related disorders among the substance abuse patients.Materials and methods:There was an observational study conducted in the drug de-addiction unit at Taif,Eradah,and Mental Health Hospital in Saudi Arabia.This study included all substance abusers admitted to the hospital who met the inclusion and exclusion criteria.The study included patients of both genders admitted to the drug de-addiction unit between April 2021 and October 2022.Based on a descriptive statistical analysis,categorical variables were presented as frequencies and percentages.Results:An observational study was conducted for nearly one and a half years.We interviewed 358 substance abuse patients following a systematic sampling procedure in a peaceful,non-threatening environment.Among the 358 substance users,353(98.60%)were male and 5(1.39%)were female.According to the survey,117(32.68%)of the participants reported abusing substances during their 31-40 years of age,followed by 102(28.49%)during their 25-30 years of age.The predominant level of substance abuse was among the unemployed 163(45.53%),followed by students 105(29.33%).It was found that 58.66%of all respondents had initiated abuse between the ages of 18-24 years of age.Conclusion:In our study,combined substances like amphetamine and cannabis abusers were most prevalent because these are the most popular illicit drugs which are easily available.Islamic culture prohibits alcohol consumption both religiously and legally,making alcohol abuse the least prevalent of all drug addictions.
基金Supported by the National Natural Science Foundation of China(Nos.31800457,32170383)。
文摘Although many studies have found that cadmium(Cd)can be toxic to microalgae,only a few reports focused on the role of extracellular polymeric substances(EPS)in Cd(Ⅱ)detoxification.The biochemical and physiological endpoints of Microcystis aeruginosa,including the composition and functional groups of soluble EPS(SL-EPS),loosely bound EPS(LB-EPS),and tightly bound EPS(TB-EPS),were detected to elucidate the toxicity and detoxification mechanisms of Cd(Ⅱ)for cyanobacteria.Toxicological and physiological assays on M.aeruginosa showed that the 0.25-mg/L Cd(Ⅱ)resulted in a larger inhibition on growth and F_(v)/F_(m).Nevertheless,Cd(Ⅱ)significantly induced much higher contents of superoxide dismutase(SOD),intracellular microcystin LR(MC-LR),extracellular MC-LR,and EPS.Scanning electron microscopy with energy dispersive X-ray spectroscopy confirmed that Cd(Ⅱ)was absorbed into the EPS layer.Fourier transform infrared spectrum analysis revealed that the functional groups bound with Cd(Ⅱ)of algae biomass,SL-EPS,LB-EPS,and TB-EPS were somewhat different.The C=O/C=N groups ofδ-lactam or protein were their prominent functional groups,suggesting that amide or proteins in the EPS played a key role in the adsorption in Cd(Ⅱ).The concentration of 0.25 mg/L of Cd(Ⅱ)may change the chemical structure of EPS by altering the production of protein-like substances containing tryptophan.This study indicated that M.aeruginosa could detoxify Cd(Ⅱ)stress via induction of antioxidant capacity(higher SOD activity and MC synthesis),EPS production,and modification in chemical structure of EPS.
文摘This essay explores the connections between Hoarding Disorder and Substance Use Disorder,two distinct mental health conditions with clear diagnostic criteria in the DSM-5.Hoarding Disorder,marked by excessive possession accumulation and difficulties in letting go,affects 2-6%of the global population,leading to severe consequences.Potential causes include genetic predisposition,neural issues,and traumatic experience.Substance Use Disorder is influenced by more societal factors.Both disorders share a comorbidity in Attention-Deficit/Hyperactivity Disorder(ADHD).Network analysis shows a strong direct relationship between Hoarding Disorder and ADHD,while social influences increase ADHD prevalence in Substance Use Disorder individuals.Moreover,both disorders benefit from Cognitive Behavioral Therapy(CBT).Exposure and Ritual Prevention effectively address hoarding symptoms,while CBT for Substance Use Disorder focuses on the interplay between thoughts,emotions,and actions.Despite being classified as a mental illness in DSM-5,Hoarding Disorder receives less attention than Substance Use Disorder.This essay aims to raise awareness of Hoarding Disorder by highlighting its commonalities with Substance Use Disorder in terms of causes,comorbidities,and treatment approaches.
基金Supported by the Youth Fund Project of the National Natural Science Foundation of China(32001570)the Post-doctorate Program Funding in Heilongjiang Province(LBH-Z19118)the Academic Backbone'Project of Northeast Agricultural University(20XG11)。
文摘Soybean is one of the important crops in China. Soymilk, a traditional neutral plant-based protein drink, is rich in high quality proteins. Although soybean milk is rich in nutrients, its marketing among consumers, especially those in Western countries who are used to peaceful flavor, has been limited due to the adverse flavor impact brought by its special composition. In recent years, with the increasing attention to the nutritional value of soymilk, the flavor of soymilk has become a popular research object for scholars at home and abroad. The flavor components of soymilk are mainly volatile small molecular compounds produced by enzymatic reactions catalyzed by lipoxygenase(LOX). After formation, they interact with protein macromolecules to form the overall flavor of soymilk. At present, there are many methods to control the off-odor of soymilk at home and abroad, including physical heating methods, chemical methods, biological enzymatic digestion methods, mask methods, and a variety of breeding methods. These methods effectively reduce the off-odor of soymilk, but all of them have shortcomings. Currently, the sensory characteristics of the beany odor in soymilk are evaluated mainly by traditional human sensory scoring along with the assistance of modern instrument analysis of volatile flavor substances using headspace solid phase microextraction(SPME) gas chromatography coupled with-mass spectrometry(GC-MS). This paper summarized the research results of volatile flavor substances in soymilk in recent years and the sensory evaluation methods of soymilk at home and abroad, and looked forward to the future development direction, hoping to provide some theoretical bases and reference detection methods for solving the problem of soymilk flavor in the future.
文摘Substance use disorders(SUDs)are a growing problem among older adults.Acamprosate,disulfiram,and naltrexone are United States Food and Drug Administration(referred to as FDA)approved for the treatment of alcohol use disorder,and buprenorphine is approved for the treatment of opiate use disorder among adults.However,the data on the use of these medications for the treatment of SUDs among older adults are unclear from randomized controlled trials(referred to as RCTs).A review of the literature indicates that there are only two RCTs that evaluated the use of pharmacologic agents for SUDs among older adults(≥50 years).One trial evaluated the use of naltrexone when compared to placebo for the treatment of alcohol use disorder among individuals,50-70 years in age.The other trial evaluated the use of naltrexone or placebo as adjuncts with sertraline in the treatment of alcohol use disorder among individuals older than 55 years in age.Both trials indicated that the use of naltrexone reduced the rates of relapse among older adults with alcohol use disorder.However,we did not identify any RCTs that studied the use of buprenorphine,acamprosate,or disulfiram for SUDs among older adults.Based on available evidence,it would be safe to conclude that limited data indicate some efficacy for naltrexone in the treatment of alcohol use disorder among older adults.However,data from controlled trials on the use of other medications that are FDA approved for the treatment of SUDs among younger adults are nonexistent among older adults with SUDs.
文摘Rhizobium tropici-derived extracellular polymeric substances (EPS) have been used in soils to enhance soil structures and mitigate soil erosions. However, information on their use to improve soil health and fertility indicators, and plant growth is limited. In a greenhouse study, we investigated their effects on some soil health, soil fertility indices, and the growth of black-eyed peas (Vigna unguiculate). Results showed that soils incubated with EPS significantly increased basal soil respiration, soil microbial biomass, permanganate oxidizable carbon (POC), and potentially mineralizable nitrogen (PMN). The EPS shifted microbial populations from bacteria to fungi and Gram (−ve) to Gram ( ve) bacteria. However, it had little or no effects on soil pH, soil organic matter (SOM), and cation exchange capacity (CEC). The EPS decreased soil moisture loss, increased soil aggregate stability, but delayed blacked-eyed peas germinations in the soils. At 0.1% (w/w) concentrations in soils, there was increase in plant root nodulations and vegetative growth. This study was carried out within 40 days of incubating soils with EPS or growing the black-eyed peas in a greenhouse study. The plant growth parameters were taken before flowering and fruiting. Further studies of the effects of incubating soils with the extracellular polymeric substances on plant growth. Soil microbial biomass, microbial diversities, and other soil fertility indices are deemed necessary.
文摘Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of metaverse development,which is considered by many as the next-generation Internet.Specifically,Web3 technologies such as smart contracts and protocols like non-fungible tokens(NFTs)have supported the immersive and content-rich experience of current Web3 metaverse projects.
基金the German Federal Ministry of Health(partially).
文摘BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocaine use.Methamphetamine-group subjects further showed a significantly lower score of conscientiousness,depressive,and psychiatric symptoms than subjects from the OSgroup.In both groups,a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment.CONCLUSION There are differences between methamphetamine users and users of other drugs,but not with regard to the effectiveness of treatment in this inpatient setting.There are differences in cognitive function and psychopathology between methamphetamine and other drugs users.The existing treatment options seem to be an effective approach in treating methamphetamine dependence.
文摘The phenomenon of electrical attraction and repulsion between charged particles is well known, and described mathematically by Coulomb’s Law, yet until now there has been no explanation for why this occurs. There has been no mechanistic explanation that reveals what causes the charged particles to accelerate, either towards or away from each other. This paper gives a detailed explanation of the phenomena of electrical attraction and repulsion based on my previous work that determined the exact wave-function solutions for both the Electron and the Positron. It is revealed that the effects are caused by wave interactions between the wave functions that result in Electromagnetic reflections of parts of the particle’s wave functions, causing a change in their momenta.
文摘Present studies in physics assume that elementary particles are the building blocks of all matter, and that they are zero-dimensional objects which do not occupy space. The new I-Theory predicts that elementary particles do indeed have a substructure, three dimensions, and occupy space, being composed of fundamental particles called I-particles. In this article we identify the substructural pattern of elementary particles and define the quanta of energy that form each elementary particle. We demonstrate that the substructure comprises two classes of quanta which we call “attraction quanta” and “repulsion quanta”. We create a model that defines the rest-mass energy of each elementary particle and can predict new particles. Lastly, in order to incorporate this knowledge into the contemporary models of science, a revised periodic table is proposed.
文摘The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.
基金The German Research Foundation (DFG-Graduiertenkolleg 366) Grant Program for the High-Level Returned Scholars fromAbroad, Ministry of Personnel of China (No. 2004-2005)
文摘For phosphorus (P) recovery from wastewater, the effect of humic substances (HS) on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate (as P) and 20 mg/L HS (as dissolved organic carbon, DOC) at a constant pH value in the range of 8.0-10.0. The concentration variations of phosphate, calcium (Ca) and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction (XRD) and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH ≥9.0, the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations ≤3.5 mg/L, and at pH ≥ 9.0 and HS concentrations ≤ 10 mg/L, the final precipitates were proved to be hydroxyapatite (HAP) by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate.
文摘Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.