Optimizing the key parameter to accelerate the recovery of AMOC under a rapid increase of greenhouse gas forcing

Atlantic Meridional Overturning Circulation(AMOC)plays a central role in long-term climate variations through its heat and freshwater transports,which can collapse under a rapid increase of greenhouse gas forcing in climate models.Previous studies have suggested that the deviation of model parameters is one of the major factors in inducing inaccurate AMOC simulations.In this work,with a low-resolution earth system model,the authors try to explore whether a reasonable adjustment of the key model parameter can help to re-establish the AMOC after its collapse.Through a new optimization strategy,the extra freshwater flux(FWF)parameter is determined to be the dominant one affecting the AMOC’s variability.The traditional ensemble optimal interpolation(EnOI)data assimilation and new machine learning methods are adopted to optimize the FWF parameter in an abrupt 4×CO_(2) forcing experiment to improve the adaptability of model parameters and accelerate the recovery of AMOC.The results show that,under an abrupt 4×CO_(2) forcing in millennial simulations,the AMOC will first collapse and then re-establish by the default FWF parameter slowly.However,during the parameter adjustment process,the saltier and colder sea water over the North Atlantic region are the dominant factors in usefully improving the adaptability of the FWF parameter and accelerating the recovery of AMOC,according to their physical relationship with FWF on the interdecadal timescale.

Learning the parameters of a class of stochastic Lotka-Volterra systems with neural networks

In this paper,we propose a neural network approach to learn the parameters of a class of stochastic Lotka-Volterra systems.Approximations of the mean and covariance matrix of the observational variables are obtained from the Euler-Maruyama discretization of the underlying stochastic differential equations(SDEs),based on which the loss function is built.The stochastic gradient descent method is applied in the neural network training.Numerical experiments demonstrate the effectiveness of our method.

Structural Modal Parameter Recognition and Related Damage Identification Methods under Environmental Excitations: A Review

Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters according to the monitoring data information in the structural health monitoring(SHM)system,so as to provide a scientific basis for structural damage identification and dynamic model modification.In view of this,this paper reviews methods for identifying structural modal parameters under environmental excitation and briefly describes how to identify structural damages based on the derived modal parameters.The paper primarily introduces data-driven modal parameter recognition methods(e.g.,time-domain,frequency-domain,and time-frequency-domain methods,etc.),briefly describes damage identification methods based on the variations of modal parameters(e.g.,natural frequency,modal shapes,and curvature modal shapes,etc.)and modal validation methods(e.g.,Stability Diagram and Modal Assurance Criterion,etc.).The current status of the application of artificial intelligence(AI)methods in the direction of modal parameter recognition and damage identification is further discussed.Based on the pre-vious analysis,the main development trends of structural modal parameter recognition and damage identification methods are given to provide scientific references for the optimized design and functional upgrading of SHM systems.

Improvement of photogrammetric joint roughness coefficient value by integrating automatic shooting parameter selection and composite error model

In order to improve the accuracy of the photogrammetric joint roughness coefficient(JRC)value,the present study proposed a novel method combining an autonomous shooting parameter selection algorithm with a composite error model.Firstly,according to the depth map-based photogrammetric theory,the estimation of JRC from a three-dimensional(3D)digital surface model of rock discontinuities was presented.Secondly,an automatic shooting parameter selection algorithm was novelly proposed to establish the 3D model dataset of rock discontinuities with varying shooting parameters and target sizes.Meanwhile,the photogrammetric tests were performed with custom-built equipment capable of adjusting baseline lengths,and a total of 36 sets of JRC data was gathered via a combination of laboratory and field tests.Then,by combining the theory of point cloud coordinate computation error with the equation of JRC calculation,a composite error model controlled by the shooting parameters was proposed.This newly proposed model was validated via the 3D model dataset,demonstrating the capability to correct initially obtained JRC values solely based on shooting parameters.Furthermore,the implementation of this correction can significantly reduce errors in JRC values obtained via photographic measurement.Subsequently,our proposed error model was integrated into the shooting parameter selection algorithm,thus improving the rationality and convenience of selecting suitable shooting parameter combinations when dealing with target rock masses with different sizes.Moreover,the optimal combination of three shooting parameters was offered.JRC values resulting from various combinations of shooting parameters were verified by comparing them with 3D laser scan data.Finally,the application scope and limitations of the newly proposed approach were further addressed.

Rockburst prediction based on multi-featured drilling parameters and extreme tree algorithm for full-section excavated tunnel faces

The suddenness, uncertainty, and randomness of rockbursts directly affect the safety of tunnel construction. The prediction of rockbursts is a fundamental aspect of mitigating or even eliminating rockburst hazards. To address the shortcomings of the current rockburst prediction models, which have a limited number of samples and rely on manual test results as the majority of their input features, this paper proposes rockburst prediction models based on multi-featured drilling parameters of rock drilling jumbo. Firstly, four original drilling parameters, namely hammer pressure (Ph), feed pressure (Pf), rotation pressure (Pr), and feed speed (VP), together with the rockburst grades, were collected from 1093 rockburst cases. Then, a feature expansion investigation was performed based on the four original drilling parameters to establish a drilling parameter feature system and a rockburst prediction database containing 42 features. Furthermore, rockburst prediction models based on multi-featured drilling parameters were developed using the extreme tree (ET) algorithm and Bayesian optimization. The models take drilling parameters as input parameters and rockburst grades as output parameters. The effects of Bayesian optimization and the number of drilling parameter features on the model performance were analyzed using the accuracy, precision, recall and F1 value of the prediction set as the model performance evaluation indices. The results show that the Bayesian optimized model with 42 drilling parameter features as inputs performs best, with an accuracy of 91.89%. Finally, the reliability of the models was validated through field tests.

GA-BP模型在HSS模型参数取值中的应用

小应变硬化土(HSS)模型可以有效反映土的压缩硬化特性和小应变特性,非常适合黄土基坑的数值模拟计算。但是,HSS模型包含了11个硬化土(HS)模型参数和2个小应变参数,而这2个小应变参数往往需要采用试验方法确定,获取过程复杂。为了探讨小应变参数的预测方法,采用经过遗传算法优化的BP神经网络模型,即GA-BP神经网络模型,首先根据预设的小应变参数水平经过数值模拟计算得到49组位移数据,然后将得到的数据用于GA-BP神经网络的训练,待GA-BP神经网络的预测误差达到要求之后,再使用实际的位移数据反演得到小应变参数,最后基于预测得到的小应变参数进行数值模拟。结果显示,GA-BP神经网络模型预测的小应变参数在基坑围护结构最大水平位移和地表最大沉降计算方面表现良好,可以应用于实际工程。

组蛋白H3K27me3修饰缺失上调弥漫型胃癌细胞中SLC7A11的表达

目的描绘弥漫型胃癌组织中组蛋白H3第27位赖氨酸的三甲基化(H3K27me3)修饰的全基因组分布图谱,通过鉴定H3K27me3所调控的关键靶基因,初步探究H3K27me3修饰重编程可能调控弥漫型胃癌细胞发生发展的作用机制。方法样本来源于2021-2023年在陆军特色医学中心消化内科内镜中心及手术室胃肠外科组接受检查或治疗的患者。共收集到正常组患者14例,其中男性6例,女性8例,平均年龄46岁;胃癌组患者14例,其中男性8例,女性6例,平均年龄63岁。采用染色质靶向剪切及转座酶技术(cleavage under target and tagmentation,CUT&Tag)捕获基因组H3K27me3修饰区域,分析H3K27me3修饰重编程特征。整合转录组(RNA‐Seq)测序数据、高通量染色体构象捕获技术(high‐throughput chromosome conformation capture,Hi‐C)及已发表的公共单细胞数据,分析H3K27me3修饰重编程在弥漫型胃癌细胞中所调控靶基因。结果CUT&Tag和RNA测序数据质量符合下游分析标准,正常胃黏膜组织和弥漫型胃癌组织的组蛋白H3K27me3修饰均主要分布于远端基因间区和内含子区。相较于正常组织,胃癌组织的H3K27me3修饰存在显著的重编程特征,表现为H3K27me3总体信号强度明显降低。其中缺失的2912个H3K27me3信号峰可能导致822个肿瘤相关基因的表达上调,这些基因中上调最显著(信号值强度的差异倍数≥2,P<0.05)的56个基因主要富集于哺乳动物雷帕霉素靶蛋白复合体1(mammalian target of rapamycin complex 1,mTORC1)信号通路,其中甲硫氨酸转运体SLC7A5和胱氨酸转运体SLC7A11在胃癌组织中的表达最高。单细胞数据提示,弥漫型胃癌组织中SLC7A11的异常高表达主要存在于肿瘤上皮细胞。利用公共数据和免疫组织化学实验进一步验证SLC7A11在弥漫型胃癌中高表达,且与胃癌患者的不良预后相关。结论组蛋白H3K27me3修饰重编程是弥漫型胃癌的重要表观遗传学特征;组蛋白H3K27me3修饰缺失可能上调肿瘤细胞SLC7A11表达,进而促进肿瘤进展。

Drilling-based measuring method for the c-φ parameter of rock and its field application

The technology of drilling tests makes it possible to obtain the strength parameter of rock accurately in situ. In this paper, a new rock cutting analysis model that considers the influence of the rock crushing zone(RCZ) is built. The formula for an ultimate cutting force is established based on the limit equilibrium principle. The relationship between digital drilling parameters(DDP) and the c-φ parameter(DDP-cφ formula, where c refers to the cohesion and φ refers to the internal friction angle) is derived, and the response of drilling parameters and cutting ratio to the strength parameters is analyzed. The drillingbased measuring method for the c-φ parameter of rock is constructed. The laboratory verification test is then completed, and the difference in results between the drilling test and the compression test is less than 6%. On this basis, in-situ rock drilling tests in a traffic tunnel and a coal mine roadway are carried out, and the strength parameters of the surrounding rock are effectively tested. The average difference ratio of the results is less than 11%, which verifies the effectiveness of the proposed method for obtaining the strength parameters based on digital drilling. This study provides methodological support for field testing of rock strength parameters.

Improvement of Cold Recycled Mixture Performance Based on Improved Density Test Method and RAP Characteristics

The available test methods for optimal moisture content of cold recycled mixture(CRM)as well as its bulk specific gravity,and theoretical maximum relative density were analyzed in this work.Some test improvements were suggested to improve test control of the CRM road performance based on the discovered flaws.Besides,the properties of reclaimed asphalt pavement(RAP),including the content of old asphalt,penetration index,passing rate of 4.75 mm sieve,and gradation change rate after extraction,were examined.The effects of RAP characteristics on splitting tensile strength,water stability,the high-and low-temperature performance of emulsified asphalt CRM were studied.The results show that the optimum moisture content of CRM should be determined when the compaction work matches the specimen’s molding work.Among the analyzed methods of bulk specific gravity assessment,the dry-surface and CoreLok methods provide more robust and accurate results than the wax-sealing method,while the dry-surface method is the most cost-efficient.The modified theoretical maximum relative density test method is proposed,which can reduce the systematic error of the vacuum test method.The following RAP-CRM trends can be observed.The lower the content of old asphalt and the smaller the change rate of gradation,the smaller the voids and the better the water stability of CRM.The greater the penetration of old asphalt,the higher the fracture work and low-temperature splitting strength.The greater the penetration,the higher the passing rate of 4.75 mm sieve after extraction,and the worse the high-temperature performance of CRM.

Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast cancer.It is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone.Although cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation.Despite recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative approach.Since CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented.Nevertheless,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone metastases.Thus,surgical removal of breast CS does not necessarily ensure patient’s long-term recovery.Moreover,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is limited.Nevertheless,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone.The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread.Clinical features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

A Novel On-Site-Real-Time Method for Identifying Characteristic Parameters Using Ultrasonic Echo Groups and Neural Network

On-site and real-time non-destructive measurement of elastic constants for materials of a component in a in-service structure is a challenge due to structural complexities,such as ambiguous boundary,variable thickness,nonuniform material properties.This work develops for the first time a method that uses ultrasound echo groups and artificial neural network(ANN)for reliable on-site real-time identification of material parameters.The use of echo groups allows the use of lower frequencies,and hence more accommodative to structural complexity.To train the ANNs,a numerical model is established that is capable of computing the waveform of ultrasonic echo groups for any given set of material properties of a given structure.The waveform of an ultrasonic echo groups at an interest location on the surface the structure with material parameters varying in a predefined range are then computed using the numerical model.This results in a set of dataset for training the ANN model.Once the ANN is trained,the material parameters can be identified simultaneously using the actual measured echo waveform as input to the ANN.Intensive tests have been conducted both numerically and experimentally to evaluate the effectiveness and accuracy of the currently proposed method.The results show that the maximum identification error of numerical example is less than 2%,and the maximum identification error of experimental test is less than 7%.Compared with currently prevailing methods and equipment,the proposefy the density and thickness,in addition to the elastic constants.Moreover,the reliability and accuracy of inverse prediction is significantly improved.Thus,it has broad applications and enables real-time field measurements,which has not been fulfilled by any other available methods or equipment.

Model Parameters Identification and Backstepping Control of Lower Limb Exoskeleton Based on Enhanced Whale Algorithm

Exoskeletons generally require accurate dynamic models to design the model-based controller conveniently under the human-robot interaction condition.However,due to unknown model parameters such as the mass,moment of inertia and mechanical size,the dynamic model of exoskeletons is difficult to construct.Hence,an enhanced whale optimization algorithm(EWOA)is proposed to identify the exoskeleton model parameters.Meanwhile,the periodic excitation trajectories are designed by finite Fourier series to input the desired position demand of exoskeletons with mechanical physical constraints.Then a backstepping controller based on the identified model is adopted to improve the human-robot wearable comfortable performance under cooperative motion.Finally,the proposed Model parameters identification and control are verified by a two-DOF exoskeletons platform.The knee joint motion achieves a steady-state response after 0.5 s.Meanwhile,the position error of hip joint response is less than 0.03 rad after 0.9 s.In addition,the steady-state human-robot interaction torque of the two joints is constrained within 15 N·m.This research proposes a whale optimization algorithm to optimize the excitation trajectory and identify model parameters.Furthermore,an enhanced mutation strategy is adopted to avoid whale evolution’s unsatisfactory local optimal value.

Two-dimensional Parameter Relationships for W UMa-type Systems Revisited

Reviewing the empirical and theoretical parameter relationships between various parameters is a good way to understand more about contact binary systems.In this investigation,two-dimensional(2D)relationships for P–MV(system),P–L1,2,M1,2–L1,2,and q–Lratiowere revisited.The sample used is related to 118 contact binary systems with an orbital period shorter than 0.6 days whose absolute parameters were estimated based on the Gaia Data Release 3 parallax.We reviewed previous studies on 2D relationships and updated six parameter relationships.Therefore,Markov chain Monte Carlo and Machine Learning methods were used,and the outcomes were compared.We selected 22 contact binary systems from eight previous studies for comparison,which had light curve solutions using spectroscopic data.The results show that the systems are in good agreement with the results of this study.

Transient elastography with controlled attenuation parameter for the diagnosis of colorectal polyps in patients with nonalcoholic fatty liver disease

BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.

荣筋拈痛方通过LncRNA H19/miR-675-3p促进软骨细胞增殖防治膝骨关节炎

目的:探究荣筋拈痛方通过调控LncRNA H19/miR-675-3p对膝骨关节炎(KOA)大鼠软骨细胞基质代谢及增殖的影响。方法:30只大鼠分为空白血清组和荣筋拈痛方含药血清组,每组15只,分别给予等量生理盐水和荣筋拈痛方药液灌胃,制备空白血清和荣筋拈痛方含药血清。提取原代软骨细胞并采用Ⅱ型胶原免疫细胞化学法和甲苯胺蓝染色进行鉴定。采用IL-1β10 ng/mL干预24 h构建软骨细胞退变模型,分为空白组、模型组和荣筋拈痛方组。观察各组软骨细胞中lncRNA H19、miR-675-3p、CollagenⅡ、Aggrecan、PCNA基因相对表达水平,CollagenⅡ、Aggrecan、PCNA蛋白表达情况,EdU细胞增殖试剂盒检测各组软骨细胞增殖情况。结果:原代软骨细胞成簇生长,胞核清晰可辨,胞浆丰富,软骨细胞活力随传代次数的增加而下降。软骨细胞细胞外基质中的CollagenⅡ被染成棕黄色,苏木素将细胞核染成蓝色;甲苯胺蓝染色后细胞整体呈现蓝紫色。与空白组比较,模型组中LncRNA H19、miR-675-3p基因相对表达水平均下降(P<0.05);与模型组比较,荣筋拈痛方组LncRNA H19、miR-675-3p基因相对表达水平上升(P<0.05)。与空白组比较,模型组CollagenⅡ、Aggrecan、PCNA基因和蛋白相对表达水平均下降(P<0.05);与模型组比较,荣筋拈痛方组CollagenⅡ、Aggrecan、PCNA基因和蛋白相对表达水平均上升(P<0.05)。与空白组比较,模型组中软骨细胞EdU阳性细胞率降低(P<0.05);与模型组比较,荣筋拈痛方组EdU阳性细胞率上升(P<0.05)。结论:荣筋拈痛方可通过上调LncRNA H19/miR-675-3p促进CollagenⅡ、Aggrecan、PCNA表达,抑制细胞外基质降解,促进软骨细胞增殖,起到治疗KOA的作用。

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

基于NLRP3/Caspase-1/GSDMD通路探讨阿霉素纳米凝胶载药对H22肝癌荷瘤小鼠的作用机制

目的通过检测NOD样受体蛋白3(NLRP3)/半胱氨酸天冬氨酸蛋白水解酶-1(Caspase-1)/消皮素D(GSDMD)通路,探讨阿霉素纳米凝胶载药(Nanogel drug loading,NG)对H22肝癌荷瘤小鼠的作用机制。方法将H22肝癌细胞珠每只1.25×106个/100μl接种于Balb/c小鼠右前肢腋窝皮下,待肿瘤体积至50~60mm3时,将40只Balb/c小鼠随机分为5组(n=8),分别为肿瘤对照组、阿霉素3mg组(DOX-3.0)、阿霉素6mg组(DOX-6.0)、阿霉素纳米凝胶载药3mg组(NG/DOX-3.0)和阿霉素纳米凝胶载药6mg组(NG/DOX-6.0)。各组均采用尾静脉注射给药治疗,分别给予生理盐水(5ml/kg)、DOX(3mg/kg)、DOX(6mg/kg)、NG/DOX(3mg/kg)和NG/DOX(6mg/kg),1次/3d,给药4次,于给药结束第3d处死动物取材。通过苏木精-伊红(hematoxylin-eosin,HE)染色,观察肿瘤生长情况和坏死面积;采用免疫组织化学染色检测NLRP3/Caspase-1/GSDMD凋亡基因的表达情况。结果HE染色与肿瘤对照组比较,各治疗组肿瘤生长状态较差,且DOX-3.0、NG/DOX-3.0、DOX-6.0、NG/DOX-6.0肿瘤坏死面积百分率依次增大,组间差异均有统计学意义(P<0.05);与肿瘤对照组比较,DOX-3.0、NG/DOX-3.0、DOX-6.0、NG/DOX-6.0组肿瘤组织中NLRP3、Caspase-1、GSDMD的蛋白阳性表达水平依次减弱,组间差异均有统计学意义(P<0.05),纳米凝胶载药组作用优于单纯阿霉素给药组。结论纳米凝胶载药组治疗H22肝癌的作用优于阿霉素单独用药,它能通过下调NLRP3/Caspase-1/GSDMD通路,有效抑制肿瘤生长、降低药物使用剂量及提高抗癌效果,具有良好发展前景,其作用机制有待于进一步探讨。

Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3

Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.

AlGaN/GaN HEMT器件有效栅长和栅宽提取

有效栅长、有效栅宽和沟道电阻等AlGaN/GaN高电子迁移率晶体管(HEMT)参数对于工艺控制和器件设计非常重要.基于AlGaN/GaN HEMT器件源漏之间的总电阻与栅长及栅宽的倒数之间的线性关系,提出了一种简单方法提取有效栅长和有效栅宽.制作了两组AlGaN/GaN HEMT器件,这两组器件的源漏间距为80μm,栅源间距为10μm.其中一组器件固定栅宽为400μm,栅长分别为10、20、30、40、50、60μm;另一组器件固定栅长为40μm,栅宽分别为200、300、400、500、600、800μm.通过研究源漏之间的总电阻随栅长和栅宽变化规律,获得栅长与有效栅长的差值为0.48989μm,栅宽与有效栅宽的差值为-11.12191μm.