Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer prog...Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer progression,therapy resistance,and metastasis.The TME is a complex ecosystem consisting of stromal and immune cells,extracellular matrix(ECM),and various signaling molecules that dynamically interact with tumor cells.Cancer-associated fibro-blasts remodel the ECM and secrete growth factors that promote tumor growth and invasion.Immune cells,such as tumor-associated macrophages,regulatory T cells,and myeloid-derived suppressor cells,often contribute to an immunosup-pressive environment that hinders anti-tumor immune responses.The ECM pro-vides structural support and acts as a reservoir for signaling molecules that in-fluence cancer cell behavior.These components evolve together with tumor cells,facilitating immune evasion,therapy resistance,and epithelial-to-mesenchymal transition,which promotes metastasis.Understanding these interactions is nece-ssary to develop novel therapeutic strategies that target both tumor and micro-environmental components.This minireview highlights the key stromal and immune elements within the breast cancer microenvironment,discussing their individual and collective roles in tumor progression and clinical outcomes,while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.展开更多
We report here arsenic speciation in 1643 freshwater fish samples,representing 14 common fish species from 53 waterbodies in Alberta,Canada.Arsenic species were extracted from fish muscle tissue.Arsenic species in the...We report here arsenic speciation in 1643 freshwater fish samples,representing 14 common fish species from 53 waterbodies in Alberta,Canada.Arsenic species were extracted from fish muscle tissue.Arsenic species in the extracts were separated using anion-exchange high-performance liquid chromatography(HPLC)and quantified using inductively coupled plasma mass spectrometry(ICPMS).The total arsenic concentrations in fish ranged from 2.8 to 1200μg/kg(in wet weight of sample)(mean 71±101μg/kg),which are all below the 2000μg/kg(wet weight)maximum allowable total arsenic in fish,recommended by the Ontario Ministry of the Environment.In 99.7%,or 1638 of all 1643 freshwater fish samples analyzed,arsenobetaine(AsB)was detectable,with concentrations higher than the method detection limit of 0.25μg/kg(wet weight).Dimethylarsinic acid(DMA)was detectable(concentration>0.25μg/kg)in 92.1%,or 1514 of the 1643 freshwater fish samples.Inorganic arsenate(iAs^(Ⅴ))was detectable(>0.25μg/kg)in 1119 fish(i.e.,68.1% of 1643 samples).Monomethylarsonic acid(MMA)was detectable(>0.25μg/kg)in 418 fish(25.4%of 1643 samples).The concentrations of arsenic species in the 1643 fish samples varied by as much as three orders of magnitude,ranging from below the method detection limit of 0.25μg/kg to the maximum concentrations of 380μg/kg for AsB,150μg/kg for DMA,70μg/kg for iAs^(Ⅴ),and 51μg/kg for MMA.AsB made up 46.1%±26.2% of total arsenic species.Arsenic speciation patterns varied between lake whitefish,northern pike,and walleye,the three most common types of fish analyzed.The relative proportion of DMA in northern pike was larger than in lake whitefish and walleye,and conversely,the relative proportion of iAs^(Ⅴ) was lower in northern pike.Seven unknown arsenic species were detected,and their chromatographic retention time did not match with those of available arsenic standards.At least one unknown arsenic species was detected in 33.4%,or 549 of 1643 freshwater fish samples.The concentrations of unknown arsenic species were as high as 61μg/kg.Future research is necessary to identify unknown arsenic species and to determine contributing factors to the observed arsenic species patterns and concentrations.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the...Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the overall prognosis for GC remains poor,primarily due to late-stage diagnosis.Current diagnostic tools,such as endoscopy and biopsy,are invasive and are often utilized only after symptoms arise,leading to missed opportunities for early intervention.Traditional serum tumour markers,such as carcinoembryonic antigen and carbohydrate antigen 19-9,demonstrate limited sensitivity and specificity,particularly in the disease's early stages.GC often diagnosed at advanced stages due to a lack of early,specific biomarkers.Chronic inflammation plays a significant role in gastric carcinogenesis,particularly in cases of Helicobacter pylori-associated gastritis.Pro-inflammatory cytokines have gained attention as potential noninvasive serum biomarkers for early diagnosis and disease monitoring.In recent years,numerous studies have explored the potential of serum cytokines-such as interleukin(IL)-6,tumour necrosis factor-alpha,IL-8 and interferon-gamma-as biomarkers for detecting gastric cancer.Future research integrating cytokine profiling with imaging,endoscopic,or genomic data may revolutionize how we screen and manage GC.展开更多
BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly di...BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.展开更多
The management of rectal lesions has been significantly enhanced by advancements in endoscopic and minimally invasive surgical techniques.Endoscopic submucosal dissection(ESD),transanal endoscopic microsurgical submuc...The management of rectal lesions has been significantly enhanced by advancements in endoscopic and minimally invasive surgical techniques.Endoscopic submucosal dissection(ESD),transanal endoscopic microsurgical submucosal dissection(TEM-ESD),and transanal minimally invasive surgery(TAMIS)offer precision and reduced morbidity for treating these conditions.This minireview evaluates the efficacy,safety,and clinical outcomes of ESD,TEM-ESD,and TAMIS,highlighting their roles in the contemporary management of rectal lesions.A desktop research study with a particular focus on ESD,TEM-ESD,and TAMIS for rectal lesions was conducted.Key outcomes assessed include complete resection rates,complication rates,recurrence rates,and functional outcomes following the procedure.ESD is noted for its high rate of en bloc resection with minimal invasiveness,suitable for large or flat lesions.TEM-ESD has demonstrated similar efficacy,with additional benefits including shorter procedure times and a more favorable learning curve,compared to traditional ESD,as evidenced by recent comparative studies.TAMIS offers a less invasive option with enhanced visualization and accessibility,supporting its use in a broader range of rectal lesion cases.ESD,TEM-ESD,and TAMIS are all effective therapeutic options for rectal lesions,each presenting unique advantages depending on lesion characteristics and patient factors.展开更多
We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresp...We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresponding extended ab initio data set,we construct interpolation formulas covering the range from low-density,high-temperature to high-density,low-temperature plasmas.Our conductivity model repro-duces the well-known limits of the Spitzer and Ziman theory.We compare with available experimental data andfind very good agreement.The new conductivity model can be applied,for example,in dynamo simulations for magneticfield generation in gas giant planets,brown dwarfs,and stellar envelopes.展开更多
Clinically significant Portal hypertension(PH),defined by a hepatic venous pressure gradient(HVPG)greater than 10 mmHg,is a key predictor of decompensation events in cirrhosis,leading to variceal hemorrhage,ascites,an...Clinically significant Portal hypertension(PH),defined by a hepatic venous pressure gradient(HVPG)greater than 10 mmHg,is a key predictor of decompensation events in cirrhosis,leading to variceal hemorrhage,ascites,and hepatic encephalopathy.This narrative review explores the pathophysiology of PH in cirrhosis,evaluates diagnostic methods for identifying clinically significant PH(CSPH),and discusses guideline-driven strategies to prevent initial and further decompensation.While HVPG remains the gold standard for diagnosing CSPH,non-invasive tools such as liver stiffness measurement and spleen stiffness measurement are increasingly used for initial risk stratification.The combined use of these tools reduces the proportion of patients in the diagnostic"grey zone".Endoscopic ultrasound-guided portal pressure gradient is an emerging diagnostic tool that requires further validation.Non-selective beta-blockers are the cornerstone of primary prophylaxis for decompensation,and their combination with endoscopic variceal ligation is the first-line therapy for secondary prophylaxis of recurrent esophageal variceal bleeding.Statins show promise in reducing PH and preventing decompensation while further studies are still needed.This review also discusses the indications for preemptive transjugular intrahepatic portosystemic shunt and its role in managing refractory ascites and variceal bleeding.展开更多
Oral and maxillofacial diagnostic imaging is of paramount importance in dental clinical diagnosis,treatment planning,and follow-up procedures.Periapical ra-diographic examination and numerous panoramic systems are use...Oral and maxillofacial diagnostic imaging is of paramount importance in dental clinical diagnosis,treatment planning,and follow-up procedures.Periapical ra-diographic examination and numerous panoramic systems are used in routine clinical dental practice.Cone beam CT is widely used and currently the method of choice in oral and maxillofacial implantology,endodontics,maxillofacial surgery,periodontics,degenerative temporomandibular joint disease,orthodontics,airway studies,sleep disorders,and forensic dentistry.Another innovative laboratory re-search tool that offers three-dimensional(3D)detailed high-resolution images of in vitro teeth and neighboring structures with submicrometric accuracy is micro-computed tomography.Ultra-high radiation doses,long scanning times,and high costs preclude its routine clinical use.In response to the high demand for a te-chnique that could provide real-time images using a cost-effective,rapid,user-friendly,and portable technique without ionizing radiation,some authors pro-posed ultrasound imaging methods as an alternative to X-ray imaging techniques.Ultrasonography can be used in the dentomaxillofacial region for various diagno-stic purposes such as salivary gland and superficial tissue examination.Recently,dedicated dental magnetic resonance imaging with appropriate software,hard-ware,sequences,and field of view tailored to fit dentomaxillofacial anatomy was introduced.Lately,3D printing technologies and their application in dentistry has attracted attention.During 3D printing a given material is added in successive layers to create a 3D object.The application of this technology has the potential to decrease operation time and minimize operator bias and the possibility of proce-dural errors.Another hot topic regarding dentomaxillofacial radiology is artificial intelligence,which is a field related to computer science dedicated to developing systems or machines that can perform tasks traditionally associated with human intelligence.It is obvious that further investigation and research in the field of dentomaxillofacial radiology will make great contributions to diagnostic imaging for various dental specialties.展开更多
A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic...A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic fusion membrane tumor vaccine,EV–CM,was successfully constructed by fusing extracellular vesicles(EVs)from S.aureus and CM from B16F10 melanoma cells.Inheriting the advantages of parental components,the EV–CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies.In vivo vaccine tests have shown that EV–CM can activate immune antitumor responses and prevent tumorigenesis.To further enhance the immunotherapeutic and antimetastatic effects of EV–CM,Pt-porphyrin coordination polymer as an immunopotentiator(CPIP)was implanted into an EV–CM nanoplatform(CPIP@EV–CM),which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions.In vitro performance tests,cell experiments,and in vivo animal models have confirmed that the CPIP@EV–CM combined with US has better ROS production,tumor cell killing,and antimetastasis abilities.The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic,self-adjuvant,and expandable vaccines,providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies,which is expected to be used as a safe and effective treatment in clinical practice.展开更多
Electrical insulation faults produce partial discharges(PD),which can be analysed to identify specific types of defects.PD clustering is a widely used method to identify PD sources,although its success depends largely...Electrical insulation faults produce partial discharges(PD),which can be analysed to identify specific types of defects.PD clustering is a widely used method to identify PD sources,although its success depends largely on the feature maps used.In this paper,three widely used feature maps,or separation maps,are compared:chromatic,energy wavelet with principal component analysis(EW-PCA),and time-frequency(TF).To compare and evaluate,five scenarios with multi-PD environments with noise were developed.The clustering ability of the maps was evaluated using two performance indicators:intercluster distance and intracluster distance.The results indicate that the EW-PCA map performed the best in all scenarios,correctly identifying the largest number of data points and producing the clearest and most distinct clusters.The TF map created distinct clusters in several scenarios,but not all.The chromatic map created distinct clusters in all scenarios but was not as well defined as the other two separation maps.Given the results,it is important in fieldwork to use a wide range of PD clustering,accompanied by performance metrics that support a less biased decision tailored to the test object.展开更多
Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were freque...Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.展开更多
The intrinsic antiferromagnetic topological insulators in the Mn-Bi-Te family,composed of superlattice-like MnBi_(2)Te_(4)/(Bi_(2)Te_(3))_(n)(n=0,1,2,3,...)layered structure,present intriguing states of matter such as...The intrinsic antiferromagnetic topological insulators in the Mn-Bi-Te family,composed of superlattice-like MnBi_(2)Te_(4)/(Bi_(2)Te_(3))_(n)(n=0,1,2,3,...)layered structure,present intriguing states of matter such as quantum anomalous Hall effect and the axion insulator.However,the surface state gap,which is the prerequisite for the observation of these states,remains elusive.Here by molecular beam epitaxy,we obtain two types of MnBi_(4)Te_(7)films with the exclusive Bi_(2)Te_(3)(BT)or MnBi_(2)Te_(4)(MBT)terminations.By scanning tunneling spectroscopy,the mass terms in the surface states are identified on both surface terminations.Experimental results reveal the existence of a hybridization gap of approximately 23 meV in surface states on the BT termination.This gap comes from the hybridization between the surface states and the spin-split states in the adjacent MBT layer.On the MBT termination,an exchange mass term of about 28±2 meV in surface states is identified by taking magnetic-field-dependent Landau level spectra as well as theoretical simulations.In addition,the mass term varies with the field in the film with a heavy BiMn doping level in the Mn layers.These findings demonstrate the existence of mass terms in surface states on both types of terminations in our epitaxial MnBi_(4)Te_(7)films investigated by local probes.展开更多
To the Editor:Hepatocellular carcinoma(HCC)represents the fifth most com-mon malignancy and the third cancer-related cause of death worldwide[1].Among several treatment modalities for HCC,liver transplantation(LT)is a...To the Editor:Hepatocellular carcinoma(HCC)represents the fifth most com-mon malignancy and the third cancer-related cause of death worldwide[1].Among several treatment modalities for HCC,liver transplantation(LT)is a preferred option for selected patients[2,3],which removes the tumor and targets the underlying liver disease simultaneously.To minimize the incidence of tumor recurrence,the Milan criteria and subsequently a series of expanded criteria such as UCSF and Hangzhou criteria were introduced[4-6].How-ever,tumor recurrence,which was partially ascribed to the im-paired function of antitumor immune responses following LT,still remains a pivotal obscure that hinders long-term survival[7,8].The human liver is characterized by a dual blood supply,with 80%of blood from the portal vein carrying bacterial endotoxin from the gastrointestinal tract.Liver is thus constantly exposed to a large load of intestinal antigens.展开更多
Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting th...Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.展开更多
In the Turkish Economy,there were radical changes in the structure of the economy with the policies of opening up to the outside world and transition to a free market economy in the 1980s,and the last step of this ope...In the Turkish Economy,there were radical changes in the structure of the economy with the policies of opening up to the outside world and transition to a free market economy in the 1980s,and the last step of this opening up and liberalization process was realized with the decision number 32 in 1989.We can say that with the liberalization of capital movements in the 1990s,economic growth and development were tried to be achieved through hot money inflows rather than direct foreign investments.This trend made the economy more open to crises,and for the first time,a crisis occurred in the form of the 1994 economic crisis,which was understood to be caused by hot money.The same economic structure experienced a financial and economic crisis caused by hot money again in November 2000 and February 2001.While the crisis was overcome with the stand-by agreement made with the IMF(International Monetary Fund)and the announced Transition to a Strong Economy program,the economy started to grow rapidly with the ease of using foreign resources,and political stability seems to have enabled this economic growth process to continue uninterruptedly except 2009.There was also a decrease in inflation rates.The same economic structure continued in the period between 2010 and 2020,and the financing need of economic growth was met by outsourcing.However,this process was different from the previous decade and there was no economic and financial crisis other than the sudden increase in exchange rates in 2018.We can say that the sudden exchange rate increase in 2018 was perceived as a harbinger of possible exchange rate shocks in the following years.展开更多
Local excision(LE)is an effective treatment option for rectal cancer that shows significant regression following neoadjuvant chemoradiotherapy.Compared to traditional total mesorectal excision(TME),LE can achieve comp...Local excision(LE)is an effective treatment option for rectal cancer that shows significant regression following neoadjuvant chemoradiotherapy.Compared to traditional total mesorectal excision(TME),LE can achieve comparable on-cological outcomes while preserving function and improving quality of life(QoL).The indications for LE have been gradually expanded,but there are uncertainties regarding postoperative oncological results.Long-term follow-up prospective randomized controlled trials comparing TME and LE in terms of both oncological outcomes and QoL could help reduce uncertainties between these two approaches and contribute to the development of evidence-based guidelines for rectal cancer treatment.展开更多
We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As...We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.展开更多
Purpose–This study aims to investigate the fatigue behavior and failure modes of bolted lap joints using Modified Tensile Specimens(MTS)under various cyclic load conditions.Emphasis is placed on identifying the relat...Purpose–This study aims to investigate the fatigue behavior and failure modes of bolted lap joints using Modified Tensile Specimens(MTS)under various cyclic load conditions.Emphasis is placed on identifying the relationship between load amplitude,fatigue life,and damage progression in low-carbon steel assemblies.Design/methodology/approach–An experimental approach was adopted using MTS specimens fabricated from St 1203 cold-rolled steel,joined with Grade 8.8 M4 bolts.Cyclic fatigue tests were conducted under zerobased loading at seven distinct force levels.Fracture surfaces were visually analyzed to identify dominant failure mechanisms.Findings–The results revealed a strong inverse correlation between applied cyclic load and fatigue life.Three distinct failure modes were identified:bolt shear at high loads(5.4 kN),interface cracking and slippage at moderate loads(4.9–5.1 kN),and plate tearing or stable fatigue behavior at lower loads(54.1 kN).The results highlight a progressive transition in failure mechanisms,from bolt shear at high loads to plate tearing and interface cracking at lower loads,providing essential insights for fatigue-resistant bolted joint design.Originality/value–This study offers original insights into the fatigue behavior of bolted lap joints using MTS,a relatively underexplored configuration in fatigue assessment.By experimentally evaluating failure modes under varied cyclic load levels,the authors uncover critical transitions in damage mechanisms—from bolt shear to interface cracking and plate tearing—depending on the applied load.Unlike many existing studies focused on numerical modeling or bonded joints alone,this work provides empirical data rooted in real-world fastening conditions using cold-rolled low-carbon steel.展开更多
Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and...Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.展开更多
文摘Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer progression,therapy resistance,and metastasis.The TME is a complex ecosystem consisting of stromal and immune cells,extracellular matrix(ECM),and various signaling molecules that dynamically interact with tumor cells.Cancer-associated fibro-blasts remodel the ECM and secrete growth factors that promote tumor growth and invasion.Immune cells,such as tumor-associated macrophages,regulatory T cells,and myeloid-derived suppressor cells,often contribute to an immunosup-pressive environment that hinders anti-tumor immune responses.The ECM pro-vides structural support and acts as a reservoir for signaling molecules that in-fluence cancer cell behavior.These components evolve together with tumor cells,facilitating immune evasion,therapy resistance,and epithelial-to-mesenchymal transition,which promotes metastasis.Understanding these interactions is nece-ssary to develop novel therapeutic strategies that target both tumor and micro-environmental components.This minireview highlights the key stromal and immune elements within the breast cancer microenvironment,discussing their individual and collective roles in tumor progression and clinical outcomes,while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.
基金supported by Alberta Health,Alberta Innovates,the Canada Research Chairs program,the Canadian Institutes of Health Research,and the Natural Sciences and Engineering Research Council of Canada.
文摘We report here arsenic speciation in 1643 freshwater fish samples,representing 14 common fish species from 53 waterbodies in Alberta,Canada.Arsenic species were extracted from fish muscle tissue.Arsenic species in the extracts were separated using anion-exchange high-performance liquid chromatography(HPLC)and quantified using inductively coupled plasma mass spectrometry(ICPMS).The total arsenic concentrations in fish ranged from 2.8 to 1200μg/kg(in wet weight of sample)(mean 71±101μg/kg),which are all below the 2000μg/kg(wet weight)maximum allowable total arsenic in fish,recommended by the Ontario Ministry of the Environment.In 99.7%,or 1638 of all 1643 freshwater fish samples analyzed,arsenobetaine(AsB)was detectable,with concentrations higher than the method detection limit of 0.25μg/kg(wet weight).Dimethylarsinic acid(DMA)was detectable(concentration>0.25μg/kg)in 92.1%,or 1514 of the 1643 freshwater fish samples.Inorganic arsenate(iAs^(Ⅴ))was detectable(>0.25μg/kg)in 1119 fish(i.e.,68.1% of 1643 samples).Monomethylarsonic acid(MMA)was detectable(>0.25μg/kg)in 418 fish(25.4%of 1643 samples).The concentrations of arsenic species in the 1643 fish samples varied by as much as three orders of magnitude,ranging from below the method detection limit of 0.25μg/kg to the maximum concentrations of 380μg/kg for AsB,150μg/kg for DMA,70μg/kg for iAs^(Ⅴ),and 51μg/kg for MMA.AsB made up 46.1%±26.2% of total arsenic species.Arsenic speciation patterns varied between lake whitefish,northern pike,and walleye,the three most common types of fish analyzed.The relative proportion of DMA in northern pike was larger than in lake whitefish and walleye,and conversely,the relative proportion of iAs^(Ⅴ) was lower in northern pike.Seven unknown arsenic species were detected,and their chromatographic retention time did not match with those of available arsenic standards.At least one unknown arsenic species was detected in 33.4%,or 549 of 1643 freshwater fish samples.The concentrations of unknown arsenic species were as high as 61μg/kg.Future research is necessary to identify unknown arsenic species and to determine contributing factors to the observed arsenic species patterns and concentrations.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
文摘Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the overall prognosis for GC remains poor,primarily due to late-stage diagnosis.Current diagnostic tools,such as endoscopy and biopsy,are invasive and are often utilized only after symptoms arise,leading to missed opportunities for early intervention.Traditional serum tumour markers,such as carcinoembryonic antigen and carbohydrate antigen 19-9,demonstrate limited sensitivity and specificity,particularly in the disease's early stages.GC often diagnosed at advanced stages due to a lack of early,specific biomarkers.Chronic inflammation plays a significant role in gastric carcinogenesis,particularly in cases of Helicobacter pylori-associated gastritis.Pro-inflammatory cytokines have gained attention as potential noninvasive serum biomarkers for early diagnosis and disease monitoring.In recent years,numerous studies have explored the potential of serum cytokines-such as interleukin(IL)-6,tumour necrosis factor-alpha,IL-8 and interferon-gamma-as biomarkers for detecting gastric cancer.Future research integrating cytokine profiling with imaging,endoscopic,or genomic data may revolutionize how we screen and manage GC.
文摘BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.
文摘The management of rectal lesions has been significantly enhanced by advancements in endoscopic and minimally invasive surgical techniques.Endoscopic submucosal dissection(ESD),transanal endoscopic microsurgical submucosal dissection(TEM-ESD),and transanal minimally invasive surgery(TAMIS)offer precision and reduced morbidity for treating these conditions.This minireview evaluates the efficacy,safety,and clinical outcomes of ESD,TEM-ESD,and TAMIS,highlighting their roles in the contemporary management of rectal lesions.A desktop research study with a particular focus on ESD,TEM-ESD,and TAMIS for rectal lesions was conducted.Key outcomes assessed include complete resection rates,complication rates,recurrence rates,and functional outcomes following the procedure.ESD is noted for its high rate of en bloc resection with minimal invasiveness,suitable for large or flat lesions.TEM-ESD has demonstrated similar efficacy,with additional benefits including shorter procedure times and a more favorable learning curve,compared to traditional ESD,as evidenced by recent comparative studies.TAMIS offers a less invasive option with enhanced visualization and accessibility,supporting its use in a broader range of rectal lesion cases.ESD,TEM-ESD,and TAMIS are all effective therapeutic options for rectal lesions,each presenting unique advantages depending on lesion characteristics and patient factors.
基金supported by the Priority Program SPP 1992 of the German Science Foundation(DFG)The Diversity of Exoplanets under project number 362460292.
文摘We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresponding extended ab initio data set,we construct interpolation formulas covering the range from low-density,high-temperature to high-density,low-temperature plasmas.Our conductivity model repro-duces the well-known limits of the Spitzer and Ziman theory.We compare with available experimental data andfind very good agreement.The new conductivity model can be applied,for example,in dynamo simulations for magneticfield generation in gas giant planets,brown dwarfs,and stellar envelopes.
基金Supported by Quebec Health Research Fund Clinician Research Scholars Junior 1,No.350546.
文摘Clinically significant Portal hypertension(PH),defined by a hepatic venous pressure gradient(HVPG)greater than 10 mmHg,is a key predictor of decompensation events in cirrhosis,leading to variceal hemorrhage,ascites,and hepatic encephalopathy.This narrative review explores the pathophysiology of PH in cirrhosis,evaluates diagnostic methods for identifying clinically significant PH(CSPH),and discusses guideline-driven strategies to prevent initial and further decompensation.While HVPG remains the gold standard for diagnosing CSPH,non-invasive tools such as liver stiffness measurement and spleen stiffness measurement are increasingly used for initial risk stratification.The combined use of these tools reduces the proportion of patients in the diagnostic"grey zone".Endoscopic ultrasound-guided portal pressure gradient is an emerging diagnostic tool that requires further validation.Non-selective beta-blockers are the cornerstone of primary prophylaxis for decompensation,and their combination with endoscopic variceal ligation is the first-line therapy for secondary prophylaxis of recurrent esophageal variceal bleeding.Statins show promise in reducing PH and preventing decompensation while further studies are still needed.This review also discusses the indications for preemptive transjugular intrahepatic portosystemic shunt and its role in managing refractory ascites and variceal bleeding.
文摘Oral and maxillofacial diagnostic imaging is of paramount importance in dental clinical diagnosis,treatment planning,and follow-up procedures.Periapical ra-diographic examination and numerous panoramic systems are used in routine clinical dental practice.Cone beam CT is widely used and currently the method of choice in oral and maxillofacial implantology,endodontics,maxillofacial surgery,periodontics,degenerative temporomandibular joint disease,orthodontics,airway studies,sleep disorders,and forensic dentistry.Another innovative laboratory re-search tool that offers three-dimensional(3D)detailed high-resolution images of in vitro teeth and neighboring structures with submicrometric accuracy is micro-computed tomography.Ultra-high radiation doses,long scanning times,and high costs preclude its routine clinical use.In response to the high demand for a te-chnique that could provide real-time images using a cost-effective,rapid,user-friendly,and portable technique without ionizing radiation,some authors pro-posed ultrasound imaging methods as an alternative to X-ray imaging techniques.Ultrasonography can be used in the dentomaxillofacial region for various diagno-stic purposes such as salivary gland and superficial tissue examination.Recently,dedicated dental magnetic resonance imaging with appropriate software,hard-ware,sequences,and field of view tailored to fit dentomaxillofacial anatomy was introduced.Lately,3D printing technologies and their application in dentistry has attracted attention.During 3D printing a given material is added in successive layers to create a 3D object.The application of this technology has the potential to decrease operation time and minimize operator bias and the possibility of proce-dural errors.Another hot topic regarding dentomaxillofacial radiology is artificial intelligence,which is a field related to computer science dedicated to developing systems or machines that can perform tasks traditionally associated with human intelligence.It is obvious that further investigation and research in the field of dentomaxillofacial radiology will make great contributions to diagnostic imaging for various dental specialties.
基金supported by the National Natural Science Foundation of China(Grant nos.82272003,82302195,and 82371976)the China Postdoctoral Science Foundation(Grant no.2024M752237)+1 种基金the Sichuan Science and Technology Program(Grant no.2024YFHZ0271)PostDoctor Research Project,Sichuan University(Grant nos.2024SCU12029 and 2023SCU12070).
文摘A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic fusion membrane tumor vaccine,EV–CM,was successfully constructed by fusing extracellular vesicles(EVs)from S.aureus and CM from B16F10 melanoma cells.Inheriting the advantages of parental components,the EV–CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies.In vivo vaccine tests have shown that EV–CM can activate immune antitumor responses and prevent tumorigenesis.To further enhance the immunotherapeutic and antimetastatic effects of EV–CM,Pt-porphyrin coordination polymer as an immunopotentiator(CPIP)was implanted into an EV–CM nanoplatform(CPIP@EV–CM),which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions.In vitro performance tests,cell experiments,and in vivo animal models have confirmed that the CPIP@EV–CM combined with US has better ROS production,tumor cell killing,and antimetastasis abilities.The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic,self-adjuvant,and expandable vaccines,providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies,which is expected to be used as a safe and effective treatment in clinical practice.
基金support of the Secretaría Nacional de Ciencia,Tecnología e Innovación(SENACYT)under Grant IDDSE19-007the Agencia Nacional de Investigación y Desarrollo(ANID)under Grants Fondecyt 1230135 and Fondef TA24I10002the Sistema Nacional de Investigación(SNI)of Panama under Grant 16-2021.
文摘Electrical insulation faults produce partial discharges(PD),which can be analysed to identify specific types of defects.PD clustering is a widely used method to identify PD sources,although its success depends largely on the feature maps used.In this paper,three widely used feature maps,or separation maps,are compared:chromatic,energy wavelet with principal component analysis(EW-PCA),and time-frequency(TF).To compare and evaluate,five scenarios with multi-PD environments with noise were developed.The clustering ability of the maps was evaluated using two performance indicators:intercluster distance and intracluster distance.The results indicate that the EW-PCA map performed the best in all scenarios,correctly identifying the largest number of data points and producing the clearest and most distinct clusters.The TF map created distinct clusters in several scenarios,but not all.The chromatic map created distinct clusters in all scenarios but was not as well defined as the other two separation maps.Given the results,it is important in fieldwork to use a wide range of PD clustering,accompanied by performance metrics that support a less biased decision tailored to the test object.
基金supported by the National Institute of Environmental Research(NIER)funded by the Ministry of Environment(No.NIER-2019-04-02-039)supported by Particulate Matter Management Specialized Graduate Program through the Korea Environmental Industry&Technology Institute(KEITI)funded by the Ministry of Environment(MOE).
文摘Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.
基金supported by the National Key R&D Program of China(Grant No.2022YFA1403102)the National Natural Science Foundation of China(Grant Nos.12474478,92065102,and 61804056).
文摘The intrinsic antiferromagnetic topological insulators in the Mn-Bi-Te family,composed of superlattice-like MnBi_(2)Te_(4)/(Bi_(2)Te_(3))_(n)(n=0,1,2,3,...)layered structure,present intriguing states of matter such as quantum anomalous Hall effect and the axion insulator.However,the surface state gap,which is the prerequisite for the observation of these states,remains elusive.Here by molecular beam epitaxy,we obtain two types of MnBi_(4)Te_(7)films with the exclusive Bi_(2)Te_(3)(BT)or MnBi_(2)Te_(4)(MBT)terminations.By scanning tunneling spectroscopy,the mass terms in the surface states are identified on both surface terminations.Experimental results reveal the existence of a hybridization gap of approximately 23 meV in surface states on the BT termination.This gap comes from the hybridization between the surface states and the spin-split states in the adjacent MBT layer.On the MBT termination,an exchange mass term of about 28±2 meV in surface states is identified by taking magnetic-field-dependent Landau level spectra as well as theoretical simulations.In addition,the mass term varies with the field in the film with a heavy BiMn doping level in the Mn layers.These findings demonstrate the existence of mass terms in surface states on both types of terminations in our epitaxial MnBi_(4)Te_(7)films investigated by local probes.
基金supported by grants from the National Natural Science Foundation of China(82300742)Zhejiang Provincial Natural Science Foundation of China(LQ22H160052).
文摘To the Editor:Hepatocellular carcinoma(HCC)represents the fifth most com-mon malignancy and the third cancer-related cause of death worldwide[1].Among several treatment modalities for HCC,liver transplantation(LT)is a preferred option for selected patients[2,3],which removes the tumor and targets the underlying liver disease simultaneously.To minimize the incidence of tumor recurrence,the Milan criteria and subsequently a series of expanded criteria such as UCSF and Hangzhou criteria were introduced[4-6].How-ever,tumor recurrence,which was partially ascribed to the im-paired function of antitumor immune responses following LT,still remains a pivotal obscure that hinders long-term survival[7,8].The human liver is characterized by a dual blood supply,with 80%of blood from the portal vein carrying bacterial endotoxin from the gastrointestinal tract.Liver is thus constantly exposed to a large load of intestinal antigens.
基金supported by the National Natural Science Foundation of China,Nos.81772453(to DX),81974358(to DX),81973157(to JZ),82173646(to JZ),82302866(to YZ)。
文摘Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.
文摘In the Turkish Economy,there were radical changes in the structure of the economy with the policies of opening up to the outside world and transition to a free market economy in the 1980s,and the last step of this opening up and liberalization process was realized with the decision number 32 in 1989.We can say that with the liberalization of capital movements in the 1990s,economic growth and development were tried to be achieved through hot money inflows rather than direct foreign investments.This trend made the economy more open to crises,and for the first time,a crisis occurred in the form of the 1994 economic crisis,which was understood to be caused by hot money.The same economic structure experienced a financial and economic crisis caused by hot money again in November 2000 and February 2001.While the crisis was overcome with the stand-by agreement made with the IMF(International Monetary Fund)and the announced Transition to a Strong Economy program,the economy started to grow rapidly with the ease of using foreign resources,and political stability seems to have enabled this economic growth process to continue uninterruptedly except 2009.There was also a decrease in inflation rates.The same economic structure continued in the period between 2010 and 2020,and the financing need of economic growth was met by outsourcing.However,this process was different from the previous decade and there was no economic and financial crisis other than the sudden increase in exchange rates in 2018.We can say that the sudden exchange rate increase in 2018 was perceived as a harbinger of possible exchange rate shocks in the following years.
文摘Local excision(LE)is an effective treatment option for rectal cancer that shows significant regression following neoadjuvant chemoradiotherapy.Compared to traditional total mesorectal excision(TME),LE can achieve comparable on-cological outcomes while preserving function and improving quality of life(QoL).The indications for LE have been gradually expanded,but there are uncertainties regarding postoperative oncological results.Long-term follow-up prospective randomized controlled trials comparing TME and LE in terms of both oncological outcomes and QoL could help reduce uncertainties between these two approaches and contribute to the development of evidence-based guidelines for rectal cancer treatment.
文摘We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.
文摘Purpose–This study aims to investigate the fatigue behavior and failure modes of bolted lap joints using Modified Tensile Specimens(MTS)under various cyclic load conditions.Emphasis is placed on identifying the relationship between load amplitude,fatigue life,and damage progression in low-carbon steel assemblies.Design/methodology/approach–An experimental approach was adopted using MTS specimens fabricated from St 1203 cold-rolled steel,joined with Grade 8.8 M4 bolts.Cyclic fatigue tests were conducted under zerobased loading at seven distinct force levels.Fracture surfaces were visually analyzed to identify dominant failure mechanisms.Findings–The results revealed a strong inverse correlation between applied cyclic load and fatigue life.Three distinct failure modes were identified:bolt shear at high loads(5.4 kN),interface cracking and slippage at moderate loads(4.9–5.1 kN),and plate tearing or stable fatigue behavior at lower loads(54.1 kN).The results highlight a progressive transition in failure mechanisms,from bolt shear at high loads to plate tearing and interface cracking at lower loads,providing essential insights for fatigue-resistant bolted joint design.Originality/value–This study offers original insights into the fatigue behavior of bolted lap joints using MTS,a relatively underexplored configuration in fatigue assessment.By experimentally evaluating failure modes under varied cyclic load levels,the authors uncover critical transitions in damage mechanisms—from bolt shear to interface cracking and plate tearing—depending on the applied load.Unlike many existing studies focused on numerical modeling or bonded joints alone,this work provides empirical data rooted in real-world fastening conditions using cold-rolled low-carbon steel.
文摘Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.
