MC-ICP-MS高阻放大器校正偏移对同位素测试的影响——以汞同位素为例

增益(Gain)校正有助于消除MC-ICP-MS不同高阻放大器之间的阻值差异,进而提高同位素分析的精度和准确度,但有关Gain的偏移和校正频率对同位素测试的影响和作用原理还缺乏系统认识。本研究结合本实验室Neptune Plus MC-ICP-MS的Gain校正数据,以实际测试的汞同位素数据为例,评估了放大器Gain校正系数偏移对同位素测试的影响。结果显示,当测试标样和样品的校正系数偏移幅度一致时,汞同位素测试结果基本无变化;当偏移幅度存在明显差异且单一放大器校正系数的相对偏移幅度超过–0.070‰~0.058‰时,汞同位素的测试结果大于分析误差。Gain校正系数单日的相对变化幅度(–0.028‰~0.028‰)可保证汞同位素测试结果小于分析误差,但长期的偏移却会导致汞同位素变化远超分析误差。此外,仪器的硬件、温度和真空度等也是Gain校正系数变化的重要影响因素,因此建议定期维护仪器,并每日进行Gain校正,以保证测试结果的稳定和准确。

梯级水库优化调度的改进ODDDP算法研究

“维数灾”问题和易陷入局部最优问题是梯级水库优化调度模型求解中的热点和难点。正交离散微分动态规划算法依据正交试验原理,解决了离散微分动态规划算法在求解水库群联合优化调度问题中的维数灾问题,但并未克服其依赖初始解质量和易陷入局部最优的缺陷。对此,借鉴入侵杂草算法空间扩散机制,引入高斯随机变量,并基于三角余弦函数的周期性质,设计提出了M-IWO-ODDDP算法,从算法全局搜索能力和搜索深度两方面,提高算法全局收敛能力。采用Schaffer、Shubert两种测试函数,分析测试了M-IWOODDDP算法的收敛性和鲁棒性。并以乌江流域11级梯级水库为例开展实例应用研究,结果表明,M-IWOODDDP寻优效果显著且对初始解质量无明显依赖性,算法收敛能力强、鲁棒性好。

术后淋巴结阴性肺浸润性黏液腺癌患者的预后预测模型

背景与目的肺浸润性黏液腺癌(invasive mucinous adenocarcinoma of the lung,IMA)是肺腺癌中一种少见且特殊的类型,该类肿瘤的特点往往是少有淋巴结转移,因此对于该类肿瘤的预后评估依靠现有的肿瘤原发灶-淋巴结-转移(tumor-node-metastasis,TNM)分期存在困难。本研究的目的是构建列线图来预测术后淋巴结阴性的IMA患者的预后。方法根据纳入标准和排除标准,回顾性分析2012年7月至2017年5月宁波大学附属李惠利医院(训练队列,n=78)和宁波市第二医院(验证队列,n=66)胸外科收治的术后病理为淋巴结阴性的IMA患者的资料,分析训练队列的临床病理特征的预后价值并建立预后预测模型,并对模型性能进行评价,最后将验证队列的数据代入进行外部验证。结果单因素分析显示肺炎型、较大的肿块、包含黏液和非黏液成分的混合型、较高的总分期是5年无进展生存期(progression-free survival,PFS)及总生存期(overall survival,OS)的影响因素。多因素分析进一步表明,影像学分型、肿块大小、黏液成分是5年PFS及OS的独立预后因素。5年PFS率和OS率分别为62.82%和75.64%,亚组的生存分析显示,肺炎型和包含黏液和非黏液成分的混合型IMA患者的5年PFS及OS分别明显低于孤立型和纯黏液型IMA患者。5年PFS和OS的Harrell’s C指数分别为0.815(95%CI:0.741-0.889)和0.767(95%CI:0.669-0.865),这两个模型的校准曲线及决策曲线分析(decision curve analysis,DCA)在两个队列中显示出良好的预测性能。结论本次基于临床病理特征构建的列线图在一定程度上可以作为IMA切除术后淋巴结阴性患者的一种有效预后预测工具。

海上风电低频输电并网技术研究现状及展望

低频输电技术在中远海域的海上风电项目中具备竞争力,并有望在未来得到广泛应用。首先基于低频输电技术原理,对低频输电技术(LFAC)在海上风电应用的适应性进行了分析,表明低频输电方案在海上风电项目中不存在障碍,但仍需进一步优化低频风电机组、交交变频器等关键设备。其次,通过对比分析高压交流、柔性直流与低频输电3种方案在全生命周期成本方面的差异,发现当下低频输电因其适度的初始投入成本、运行成本与废弃成本,较高故障成本与低维护成本而在离岸距离75~300 km的中远海域具有明显经济优势。然后,参照工频交直流输电可靠性评估方法,低频输电方案可靠性需按不同模块分别进行评估,通过比较低频输电方案较其他方案在可靠性评估中的差异,表明风电机组、集电系统与输电线缆的可靠性差异来源于低频运行状态或低频设备的规格差异,而海上平台可靠性差异来源于电气设备链接方式与结构差异。最后,就低频输电技术在技术性、经济性、可靠性、风险性以及环境影响方面的未来研究提出展望。本研究旨在补充低频输电技术的理论研究基础,为低频输电技术在海上风电项目中广泛铺开做好理论准备。

A frequency servo SoC with output power stabilization loop technology for miniaturized atomic clocks

A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL)technique,incorporating an off-chip power detector(PD),ensures that the output power of the FS-SoC remains stable,mitigating the impact of power fluctuations on the atomic clock's stability.Additionally,a one-pulse-per-second(1PPS)is employed to syn-chronize the clock with GPS.Fabricated using 65 nm CMOS technology,the measured phase noise of the FS-SoC stands at-69.5 dBc/Hz@100 Hz offset and-83.9 dBc/Hz@1 kHz offset,accompanied by a power dissipation of 19.7 mW.The Cs atomic clock employing the proposed FS-SoC and PSL obtains an Allan deviation of 1.7×10^(-11) with 1-s averaging time.

Ultra-Robust and High-Performance Rotational Triboelectric Nanogenerator by Bearing Charge Pumping

As an emerging technology to convert environmental high-entropy energy into electrical energy,triboelectric nanogenerator(TENG)has great demands for further enhancing the service lifetime and output performance in practical applications.Here,an ultra-robust and high-performance rotational triboelectric nanogenerator(R-TENG)by bearing charge pumping is proposed.The R-TENG composes of a pumping TENG(P-TENG),an output TENG(O-TENG),a voltage-multiplying circuit(VMC),and a buffer capacitor.The P-TENG is designed with freestanding mode based on a rolling ball bearing,which can also act as the rotating mechanical energy harvester.The output low charge from the P-TENG is accumulated and pumped to the non-contact O-TENG,which can simultaneously realize ultralow mechanical wear and high output performance.The matched instantaneous power of R-TENG is increased by 32 times under 300 r/min.Furthermore,the transferring charge of R-TENG can remain 95%during 15 days(6.4×10^(6)cycles)continuous operation.This work presents a realizable method to further enhance the durability of TENG,which would facilitate the practical applications of high-performance TENG in harvesting distributed ambient micro mechanical energy.

Improving model performance in mapping cropland soil organic matter using time-series remote sensing data

Faced with increasing global soil degradation,spatially explicit data on cropland soil organic matter(SOM)provides crucial data for soil carbon pool accounting,cropland quality assessment and the formulation of effective management policies.As a spatial information prediction technique,digital soil mapping(DSM)has been widely used to spatially map soil information at different scales.However,the accuracy of digital SOM maps for cropland is typically lower than for other land cover types due to the inherent difficulty in precisely quantifying human disturbance.To overcome this limitation,this study systematically assessed a framework of“information extractionfeature selection-model averaging”for improving model performance in mapping cropland SOM using 462 cropland soil samples collected in Guangzhou,China in 2021.The results showed that using the framework of dynamic information extraction,feature selection and model averaging could efficiently improve the accuracy of the final predictions(R^(2):0.48 to 0.53)without having obviously negative impacts on uncertainty.Quantifying the dynamic information of the environment was an efficient way to generate covariates that are linearly and nonlinearly related to SOM,which improved the R^(2)of random forest from 0.44 to 0.48 and the R^(2)of extreme gradient boosting from 0.37to 0.43.Forward recursive feature selection(FRFS)is recommended when there are relatively few environmental covariates(<200),whereas Boruta is recommended when there are many environmental covariates(>500).The Granger-Ramanathan model averaging approach could improve the prediction accuracy and average uncertainty.When the structures of initial prediction models are similar,increasing in the number of averaging models did not have significantly positive effects on the final predictions.Given the advantages of these selected strategies over information extraction,feature selection and model averaging have a great potential for high-accuracy soil mapping at any scales,so this approach can provide more reliable references for soil conservation policy-making.

Understanding the combustion behavior of electric bicycle batteries and unveiling its relationship with fire extinguishing

In this study,a detailed analysis of the combustion behaviors of the lithium iron phosphate(LFP)and lithium manganese oxide(LMO)batteries used in electric bicycles was conducted.This research included quantitative measurements of the combustion duration,flame height,combustion temperature,heat release rate,and total heat release.The results indicated that LMO batteries exhibited higher combustion temperatures of 600–700°C,flame heights of 70–75 cm,a significantly higher heat release rate of40.1 k W(12 Ah),and a total heat release of 1.04 MJ(12 Ah)compared to LFP batteries with the same capacity.Based on these experimental results,a normalized total heat release(NORTHR)parameter was proposed,demonstrating good universality for batteries with different capacities.Utilizing this parameter,quantitative calculations and optimization of the extinguishing agent dosage were conducted for fires involving these two types of batteries,and the method was validated by extinguishing fires for these two types of battery packs with water-based extinguishing fluids.

Terahertz high-sensitivity SIS mixer based on Nb–AlN–NbN hybrid superconducting tunnel junctions

The terahertz band,a unique segment of the electromagnetic spectrum,is crucial for observing the cold,dark universe and plays a pivotal role in cutting-edge scientific research,including the study of cosmic environments that support life and imaging black holes.High-sensitivity superconductor–insulator–superconductor(SIS)mixers are essential detectors for terahertz astronomical telescopes and interferometric arrays.Compared to the commonly used classical Nb/AlO_(x)/Nb superconducting tunnel junction,the Nb/AlN/NbN hybrid superconducting tunnel junction has a higher energy gap voltage and can achieve a higher critical current density.This makes it particularly promising for the development of ultra-wideband,high-sensitivity coherent detectors or mixers in various scientific research fields.In this paper,we present a superconducting SIS mixer based on Nb/AlN/NbN parallel-connected twin junctions(PCTJ),which has a bandwidth extending up to490 GHz–720 GHz.The best achieved double-sideband(DSB)noise temperature(sensitivity)is below three times the quantum noise level.

Review on the plastic instability of medium -Mn steels for identifying the formation mechanisms of Lüders and Portevin -Le Chatelier bands

Plastic instability,including both the discontinuous yielding and stress serrations,has been frequently observed during the tensile deformation of medium-Mn steels(MMnS)and has been intensively studied in recent years.Unfortunately,research results are controversial,and no consensus has been achieved regarding the topic.Here,we first summarize all the possible factors that affect the yielding and flow stress serrations in MMnS,including the morphology and stability of austenite,the feature of the phase interface,and the deformation parameters.Then,we propose a universal mechanism to explain the conflicting experimental results.We conclude that the discontinuous yielding can be attributed to the lack of mobile dislocation before deformation and the rapid dislocation multiplication at the beginning of plastic deformation.Meanwhile,the results show that the stress serrations are formed due to the pinning and depinning between dislocations and interstitial atoms in austenite.Strain-induced martensitic transformation,influenced by the mechanical stability of austenite grain and deformation parameters,should not be the intrinsic cause of plastic instability.However,it can intensify or weaken the discontinuous yielding and the stress serrations by affecting the mobility and density of dislocations,as well as the interaction between the interstitial atoms and dislocations in austenite grains.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

Probiotics administration alleviates cognitive impairment and circadian rhythm disturbance induced by sleep deprivation

Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the Bifidobacterium breve strain(CCFM1025)were assessed in sleep-deprived mice.CCFM1025 improved the body weight and food and water intake of the mice.It also alleviated SD-induced cognitive behavioural abnormalities(in the novel object recognition test),but did not show beneficial effects on mood-and spatial memory-related behaviours.CCFM1025 significantly altered the gut microbial composition and genome function.Key microbial metabolites that may regulate sleep function were also identified,such as isovaleric acid andγ-aminobutyric acid in the gut and purine metabolites in the serum.Those metabolites may participate in gutbrain communication by acting on the striatal melatonin system,for example to increase melatonin levels,and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1.Collectively,administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites.These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

Toughening ultrastrong low-density steel by textured δ-ferrite lamellas

By both the Charpy V-notched impact and the projectile tests, we here investigated the dynamic fracture behavior of a recently developed ultrastrong lightweight steel comprising a hierarchical martensitic matrix, dispersed ultra-fine-retained austenite grains and oriented δ-ferrite lamellas, the latter being due to high Al and Si contents employed for low-density design. This steel shows a superior combination of specific ultimate tensile strength and impact toughness to other ultrastrong steels and has successfully arrested a real steel-cored bullet shot. These are attributed to the densely textured δ-ferrite lamellas that can deflect the propagating cracks until they are trapped and enclosed besides austenite-to-martensite transformation crack closure, leading to more energy consumed before failure. These results suggest a new pathway for toughening ultrastrong lightweight steels.

A Quick Calculation Method for Radiation Pattern of Submillimeter Telescope with Deformation and Displacement

Radiation pattern captures the electromagnetic performance of reflector antennas,which is significantly affected by the deformation of the primary reflector due to gravity and the displacement of the secondary reflector.During the design process of large reflector antennas,a substantial amount of time is often dedicated to iteratively adjusting structural parameters and validating electromagnetic performance.To improve the efficiency of the design process,we first propose an approximate calculation method of optical path difference(OPD)for the deformation of the primary reflector under gravity and the displacement of the secondary reflector.Then an OPD fitting function based on the modified Zernike polynomials is proposed to capture the phase difference of radiation over the aperture plane,based on which the radiation pattern will be obtained quickly by the aperture field integration method.Numerical experiments demonstrate the effectiveness of the proposed quick calculation method for analyzing the radiation pattern of a 10.4 m submillimeter telescope antenna at its highest operating frequency of 856 GHz.In comparison with the numerical simulation method based on GRASP(which is an antenna electromagnetic analysis tool combining physical optics(PO)and physical theory of diffraction(PTD)),the quick calculation method reduces the time for radiation pattern analysis from more than one hour to less than two minutes.Furthermore,the quick calculation method exhibits excellent accuracy for the figure of merit(FOM)of the radiation pattern.Therefore,the proposed quick calculation method can obtain the radiation pattern with high speed and accuracy.Compared to the time-consuming numerical simulation method(PO and PTD),it can be employed for quick analysis of the radiation pattern for the lateral displacement of the secondary reflector and the deformation of the primary reflector under gravity in the design process of a reflector antenna.

Disturbance Observer-based Pointing Control of Leighton Chajnantor Telescope

Leighton Chajnantor Telescope(LCT), i.e., the former Caltech Submillimeter Observatory telescope, will be refurbished at the new site in Chajnantor Plateau, Chile in 2023. The environment of LCT will change significantly after its relocation, and the telescope will be exposed to large wind disturbances directly because its enclosure will be completely open during observation. The wind disturbance is expected to be a challenge for LCT's pointing control since the existing control method cannot reject this disturbance very well. Therefore, it is very necessary to develop a new pointing control method with good capability of disturbance rejection. In this research, a disturbance observer—based composite position controller(DOB-CPC) is designed, in which an H∞feedback controller is employed to compress the disturbance, and a feedforward linear quadratic regulator is employed to compensate the disturbance precisely based on the estimated disturbance signal. Moreover, a controller switching policy is adopted, which applies the proportional controller to the transient process to achieve a quick response and applies the DOB-CPC to the steady state to achieve a small position error. Numerical experiments are conducted to verify the good performance of the proposed pointing controller(i.e., DOB-CPC) for rejecting the disturbance acting on LCT.

BnaWRKY75 positively regulates the resistance against Sclerotinia sclerotiorum in ornamental Brassica napus

With the development of tourism at home and abroad,Rapeseed(Brassica napus)has become an important ornamental plant.However,its ornamental value at the inflorescence stage is greatly reduced by Sclerotinia sclerotiorum.Identification of important genes in the defense responses is critical for molecular breeding,which is an important strategy for controlling the disease.In this study,we isolated a B.napus WRKY transcription factor gene,BnaWRKY75.BnaWRKY75 was found to encode a nucleus-localized protein and exhibited relatively high expression in the stems.Arabidopsis thaliana transgenic plants expressing BnaWRKY75 showed enhanced resistance to S.sclerotiorum,and both ProBnaWRKY75:GUS and gene expression analyses showed that BnaWRKY75 was highly responsive to S.sclerotiorum infection,indicating the involvement of BnaWRKY75 in response to this infection.Furthermore,overexpression(OE)of BnaWRKY75 in B.napus significantly enhanced the resistance to S.sclerotiorum,whereas the resistance was reduced in RNAi transgenic B.napus plants.Moreover,the BnaWRKY75-OE B.napus plants exhibited constitutive activation of salicylic acid-,jasmonic acid-,and ethylene-mediated defense responses and the inhibition of both H_(2)O_(2)and O_(2)·^(-)accumulation in response to this pathogen.By contrast,BnaWRKY75-RNAi plants showed a reverse pattern,suggesting that BnaWRKY75 is involved in hormonal signaling pathways and in the control of reactive oxygen species accumulation.In conclusion,these data indicate that BnaWRKY75,a regulator of multiple defense responses,positively regulates resistance against S.sclerotiorum,which may guide the improvement of resistance in rapeseed.

Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids:A case report

BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis.

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts

BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.