Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Stability analysis of intermittently jointed rock slopes based on the stepped failure mode

In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.

Role of Oncostatin M in the prognosis of inflammatory bowel disease: A meta-analysis

BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.

Assessment of the Recent Hydromorphological Features of Nokoue Lake and Its Channels (South-East Benin)

Based on 2022 and 2023 hydrometric data and satellite images (Sentinel 2022, SPOT 2010), this study aims to present the Nokoué Lake and its channels’ re-cent hydromorphological characteristics. Integrating flow, tributary morphology, and topography data determined specific power values along the axes studied. The values obtained range from 2.69 to 12.92 W/m2 for Ouémé River and 2.46 to 10.99 W/m2 for Sô River. The resulting water erosion on banks and bottoms is of linear, areolar, or gully and claw types. Lake bathymetry varies from -0.5 to -2.6 m (low flow period) and -1 to -4 m;in the Ouémé, Sô, and Totchè rivers, it varies from -5 m to -7 m, reaching -10 m at the Cotonou channel entrance (flood period). Bathymetric profiles reveal varied “U”, “V” and “Intermediate” bottom morphologies, influenced by erosion/sedimentation processes and human activities. The flow facies identified are lentic in the northern tributaries and lotic in the Cotonou and Totchè canals. Spatial analysis identified nine (09) thematic classes. In 2022, the surface area of the water body has increased from 274 km2 at low water to 280 km2 at high water, whereas in 2010 (a recent year of exceptional flooding), the surface area was 270 km2 at low water and 277 km2 at high water. Significant changes in land use are observed between 2010 and 2022. The floodplain area decreased slightly, from 421 km2 in 2010 (year of exceptional flooding) to 419 km2 in 2022. The evolution of land use shows a progressive expansion of the urban environment to the detriment of the natural environment. In the medium to long term, this trend could threaten the hydromorphological balance and even the existence of this important lagoon ecosystem.

Treatment of Vulvovaginal Candidiasis with A Strategy Based on Phototherapy (M.A.C.® Scar Acceleration Method)

Candidiasis, also known as candidiasis vulvovaginitis, is an infection caused by different types of Candida fungi, the most frequent being Candida albicans. The present study reports an effective strategy, which opens new avenues for the treatment of this public health problem. The MAC® Methodology, conventional laser light-emitting (LLLT)/LED) methods are based on the biphasic response demonstrated many times in LLLT research and as with other forms of drugs, a “drug” (irradiation parameters) and a “dose” (irradiation times) and the “Arndt-Schulz Law” is often cited as a suitable model to describe the dose-dependent effects of LLLT. This method uses photopharmaceuticals, cell markers and the use of correct parameters for each case to induce the acceleration of tissue repair. The present study shows a case of a 32-year-old patient diagnosed with recurrent candidiasis 4 years ago. Eighteen sessions were performed (every other day) using a photoactivated component (Methylene blue 1% + Clotrimazole 1%) and LED phototherapy (red, blue and violet) with emission times of 60 - 260 seconds for each applicator, according to the dose recommendations of the scar acceleration method (MAC®). At the sixth treatment session there was a noticeable decrease in the itching sensation reported by the patient. In session 11 she reported feeling a great improvement, indicating that she no longer felt itching in any area after 18 sessions. The present case demonstrates new methodologies to treat common problems in the population that have a positive impact on the quality of life. This methodology has a promising future because it is non-invasive and requires a great biological transformation for inflammatory, fungal and viral control.

“1M3S”护理管理模式对ICU急性心肌梗死患者并发症及不良心血管事件发生率的影响

目的 探讨ICU收治的急性心肌梗死患者应用“1M3S”护理管理模式所取效果,评估对并发症及不良心血管事件发生率产生的影响。方法 随机抽检2022年6月至2023年6月入住于ICU的82例急性心肌梗死患者为研究对象,利用随机数字表法将纳选对象划分为两组,应用常规护理模式的患者命名为对照组,执行“1M3S”护理管理模式的患者设定为观察组,评估两种护理模式应用优势以及干预效果。结果 观察组并发症、不良心血管事件发生率测定结果低于对照组,分别为12.19%、31.71%(P<0.05);各项护理管理质量评分测定结果呈现为观察组均高于对照组(P<0.05);相较于对照组,观察组疾病不确定感均较低(P<0.05)。结论 ICU收治的急性心肌梗死患者护理管理期间应用“1M3S”护理管理模式可以提高整体护理管理效果,在预防并发症以及不良心血管事件方面具有突出效果,有利于减轻疾病不确定感,值得借鉴。

Growth of the Earthworm Millsonia omodeoi and Its Capacity to Accumulate Five Heavy Metals (HM) in Soils along a Toll Highway in Côte d’Ivoire

The roads in correlation with the traffic linked to their existences are at the origin of the emission of numerous polluting substances likely to induce disturbances of the growth and the behavioral changes in the organisms living in their vicinities. The purpose of this study is to analyze the growth and capacity accumulation of a common earthworm species (Millsonia omodeoi) in Cu, Cr, Ni, Pb and Zn in soils along a main road called “Autoroute du Nord” in C?te d’Ivoire. Thus, the earthworms were harvested in soils from a distance of 0 m (just after the sidewalk) to a distance of 200 m from the toll highway and in a control soil sampled in Lamto reserve (C?te d’Ivoire). The study was carried out in the soil laboratory at the ecological station of Lamto reserve. The Ford-Walford technique was used to determine the model and parameters most appropriated for describing the growth of earthworms. A pairwise comparison of the growth parameters was carried out using the Kruskal-Wallis test with the STATISTICA 7.1 software. The heavy metals contained in the cultivated soils and earthworms were detected and quantified using a Scanning Electron Micro-scope (MEB FEG Supra 40 VP Zeiss) and an Atomic Absorption Spectrometer SPECTRA 110 (VARIAN). The capacity accumulation of heavy metals in earthworm was determined by the bioaccumulation factor (BAF) calculation. The results of this study showed that Gompertz is the most appropriated model to describe the growth of M. omodeoi. The life cycle of M. omodeoi shows that this earthworm adopts a K type demographic strategy. Cu is the most accumulated heavy metals in M. omodeoi, when Cr is the least accumulated. Concerning heavy metal content in the earthworms, it decreases while moving away from the pavement. These results highlight a possibility of choice of M. omodeoi as 1) indicators of heavy metals pollution and 2) target of biological organisms for environmental impact studies.

基于GNSS的2023年2月23日塔吉克斯坦M_(S)7.2地震前异常资料变化特征研究

为了进一步探究中强地震发生前GNSS坐标时序中是否存在中短期异常现象,通过分析2023年2月23日塔吉克斯坦M_(S)7.2地震前后中国大陆构造环境监测网络(简称:“陆态网络”)塔什库尔干、布伦口GNSS基准站观测资料的变化特征,发现该地震震前塔什库尔干、布伦口均出现较为明显的GNSS基准站时间序列异常现象,震前EW向存在趋势性W向运动,震后E向加速;震前NS向趋势性S向运动,临震前状态快速改变,布伦口在震后还显示出7.3 mm的EW向永久性形变,研究结果表明GNSS在地震发生短临阶段具有重要的预测意义。与2015年12月7日塔吉克斯坦M S7.4地震进行对比发现,两次M S≥7.0地震对塔什库尔干、布伦口基准站的影响差异较大。2015年12月7日塔吉克斯坦M S7.4地震为左旋走滑,影响方向主要为NE向,而2023年2月23日塔吉克斯坦M_(S)7.2地震为右旋走滑,影响方向主要为SE向。震前基线均有挤压缩短的前兆异常显示。梳理站点异常出现情况,发现异常持续时间越长、异常出现次数越多,发震震级可能越大。

非线性M-C强度准则下预应力锚索加固边坡时效稳定性分析M-P法

拓展传统极限平衡方法在复杂条件下边坡稳定性分析中的适用性一直是岩土工程界的研究热点。众所周知,边坡岩土体剪切失效一般服从于非线性强度准则,而传统极限平衡方法仅适用于线性强度准则下边坡稳定性分析。此外,预应力锚索作为一种主动防护措施,可极大地即时提高边坡稳定性而被广泛应用于中、大型边坡工程加固。然而,在应力松弛、蠕变效应以及腐蚀环境影响下预应力锚索加固边坡稳定性时效特征往往被忽视。由此,基于Morgenstern-Price(M-P)法,嵌入非线性Mohr-Coulomb(M-C)强度准则,并融入应力松弛与蠕变效应下锚索预应力损失模型以及腐蚀环境下锚索性能劣化模型,从而,建立非线性强度准则下预应力锚索加固边坡安全系数时程表达式。进一步,为了解决非线性强度准则下隐式嵌套公式难以求解的问题,归零化条间法向力初始值,并应用迭代循环求解策略,在引入循环终止允许误差判别条件后,可实现边坡稳定性理论真实结果的逼近求解。经过后续算例对比分析,验证了所提方法的可行性和合理性,与此同时,还研究了不同预应力损失速率和不同锈蚀环境下预应力锚索加固边坡稳定性的时效变化规律。

儿童支原体肺炎检测中CRP、IgM、IgG、PCT指标的临床意义分析

目的探讨在儿童支原体肺炎检测中C反应蛋白(C-reactive Protein,CRP)、免疫球蛋白指标M(Immunoglobulin M,IgM)、免疫球蛋白指标G(IgG)、降钙素原(Procalcitonin,PCT)指标的临床意义。方法选取2019年11月—2022年4月赣榆区人民医院收治的支原体肺炎患儿120例作为观察组,并在同期体检健康儿童中选取120例作为对照组,均接受CRP、IgM、IgG、PCT等指标检测,根据其检测水平进行分析。结果观察组患儿的CRP为(15.35±3.08)mg/L、PCT为(0.66±0.11)ng/L,比对照组CRP的(4.08±0.72)mg/L、PCT(0.31±0.06)ng/L高,差异有统计学意义(t=39.031、30.599,P均<0.05);观察组中急性期患儿的CRP、PCT指标水平明显高于恢复期患儿指标水平,差异有统计学意义(P均<0.05);观察组患儿的IgM、IgG、IgE水平较对照组高,IgA水平较对照组低,差异有统计学意义(P均<0.05)。结论支原体肺炎患儿接受免疫球蛋白指标、CRP、PCT指标检测,其指标值可良好地反映患儿病情,IgA水平较低,其他指标均升高,因此对以上指标进行密切监测,为支原体肺炎疾病诊断、治疗提供数据参考。

深度小于30 m正常停钻V_(S30)预测公式精度分析

我国钻孔测速中在正常停孔条件下产生大量深度小于30 m的钻孔数据。由于正常停钻,我国几乎没有此类场地下深度超30 m的钻孔实测数据,故无法以同类场地大于30 m数据直接回归V_(S30)公式。国外区域数据建立的V_(S30)预测公式有区域性,其在场地特征类似才适用;针对我国深度小于30 m正常停孔下V_(S30)预测线性外插公式LEE为具有潜在可行性公式。因此,为了从已有公式中得到可靠的V_(S30)预测公式,基于地质宏观类比,在停钻深度没有到30 m数据条件下发展了对已有公式的精度分析方法。通过对平均剪切波速竖向分布特点的分析,提出“精度分析区间”;并在缺乏停钻深度到30 m直接验证数据的前提下,提出两种分析公式预测精度的方法:方法一中校核对象是实测数据,具有一定直接检验的特点,但仅适用于具有反算能力的公式;方法二是基于所有公式都具有的——换算深度越靠近30 m则V_(S30)预测越准确的特点提出的,适用范围广。以滇中引水工程为案例,应用两种方法于该工程中深度小于30 m的正常停钻数据,为该工程选出精度最高公式LEE。

m1A/m5C/m6A/m7G调控基因预测胃癌预后及免疫关联性

目的基于m1A/m5C/m6A/m7G甲基化调控基因建立胃癌预后风险预测模型,并分析该模型与免疫的关联性。方法通过癌症基因组图谱(TCGA)-胃癌数据集筛选表达具有显著差异的m1A/m5C/m6A/m7G调控基因,通过单基因Cox回归分析和LASSO算法构建预后风险评分(risk score,RS)模型,使用Kaplan-Meier(K-M)统计进行RS模型验证,并应用细胞系进行RT-qPCR验证。利用单因素、多因素Cox回归分析建立nomogram模型。使用CIBERSORT算法和estimate包进行免疫关联性分析。结果建立了基于八个甲基化调控基因的预后RS模型,将胃癌患者分为高风险和低风险。这八个基因在胃癌细胞系中高表达(P<0.05)。在TCGA-胃癌训练集和GSE62254-验证集中,患者总生存率(OS)与分组状态之间存在显著相关性(P<0.001)。nomogram生存模型预测的1年(C-index=0.703)、3年(C-index=0.729)和5年(C-index=0.734)生存率与实际生存率的一致性较好。免疫关联性分析表明,与低风险患者组相比,高风险患者组免疫评分和免疫检查点相关基因的表达较高(P<0.05)。结论基于m1A/m5C/m6A/m7G调控基因的预后RS模型可预测胃癌预后并指导个体免疫治疗决策。

二烯丙基二硫通过磷酸化Chk1负调控Cdc25C/CyclinB1/CDK1通路阻滞白血病K562细胞G_(2)/M期

目的:研究二烯丙基二硫(diallyl disulfide,DADS)诱导人白血病K562细胞周期阻滞及其分子机制。方法:采用CCK-8、细胞计数及流式细胞术观察DADS对K562细胞增殖与周期阻滞效应。Western Blot检测DADS对K562细胞PCNA、Chk1/2以及下游分子Cdc25C、CyclinB1与CDK1表达的影响。结果:CCK-8检测显示,15μmol/L、30μmol/L、60μmol/L、120μmol/L、240μmol/L DADS处理后,呈浓度依赖性抑制K562细胞增殖,抑制率分别为32.48%、59.34%、66.42%、77.06%、81.05%(P<0.05)。对照组与Tween80组无抑制作用(P>0.05)。细胞计数结果显示,30μmol/L、60μmol/L与120μmol/L DADS处理K562细胞后,群体倍增时间分别为22.71±0.29、36.69±0.93与73.02±0.87呈浓度依赖性增加(P<0.05),而Tween80组与对照组无明显差异(P>0.05)。流式细胞术检测显示,60μmol/L与120μmol/L DADS作用K562细胞24 h与48 h后,G_(2)/M期百分率分别增加到17.6%与28.5%和18.6%与34.4%,较对照组有显著性差异(P<0.05)。60μmol/L DADS作用K562细胞1 h、2 h、4 h、8 h和24 h后,PCNA表达呈时间依赖性表达下调(P<0.05)。p-Chk1表达呈时间依赖性上调(P<0.05),而Chk1、Chk2与p-Chk2表达无明显差异(P>0.05)。并且,Cdc25C、CyclinB1和CDK1分别呈时间依赖性下调(P<0.05),但是,14-3-3蛋白无明显改变(P>0.05)。结论:DADS可磷酸化Chk1通过Cdc25C/CyclinB1/CDK1通路抑制K562细胞增殖与阻滞G_(2)/M期。

指数有界双连续n阶m次积分C群的指数公式

利用经典算子半群理论中的研究方法,基于指数有界双连续n阶m次积分C群和预解式的定义,给出指数有界双连续n阶m次积分C群与其预解式间积分的表示关系,得到指数有界双连续n阶m次积分C群的指数公式,从而推广了n阶m次积分C半群的相关结果,丰富了算子半群理论的研究内容.

P/M和W/C对磷酸镁水泥强度的影响分析

为探究磷镁比(P/M)及水灰比(W/C)对磷酸镁水泥强度的影响和作用机理,对其力学性能进行测试,并结合XRD、SEM和FT-IR等测试手段对其物相组成及微观形貌进行表征和分析。研究结果表明:W/C=0.15时,磷酸二氢钾掺量的降低会使磷酸镁水泥的各龄期抗压强度增强,P/M=1:4时其3 h强度超过30 MPa,而当掺量过高时,3 h强度低于20 MPa,其产物MgKPO_(4)·6H_(2)O(K-struvite)的生成量减少且试件存在开裂区域;W/C=0.25时,减少MgO的掺量可以提高磷酸镁水泥的强度,P/M=1:1.5时,3 h的抗压强度接近30 MPa,磷酸镁水泥的水化产物K-struvite形貌结晶完好且排列紧密。

2024年1月23日新疆阿克苏地区乌什县M S7.1地震对周围断层的应力影响及对余震的触发作用

为研究2024年新疆阿克苏地区乌什县M S7.1大震对周边区域应力的影响,基于美国地质调查局(USGS)给出的主震破裂模型,计算此次地震对周边地区产生的同震位移场及应变场,结果发现:体应变在震源西北侧呈现拉张,东南侧呈现挤压;面应变的分布与体应变的形态基本相似。为研究该地震对余震的触发情况,首先需要确定接收断层的断层面参数,对中国地震台网发布的2024年1月23日到2024年4月10日的余震震源机制节面聚类分析,得到两簇结果,选择标准差较小的二簇节面进行平均,得到走向为243.91°,倾角为64.97°;将乌什地震震源区的构造应力场投影到该发震断层上,得到滑动角为61.02°。将这些参数作为余震接收断层的断层面参数,同样基于USGS给出的主震断层破裂模型,计算主震产生的静态库仑应力,研究发现:区内库仑应力均超过0.01 MPa阈值,且库仑破裂应力最大值达0.3 MPa,大多数余震处于库仑应力变化的高值区;表明主震产生的静态库仑应力促进了余震的发生。为研究该地震发生对周围断层的影响,根据前人给出的周边断层的几何和滑动特性,计算在周边断裂上沿滑动方向上的库仑破裂应力变化,研究发现:本次地震对迈丹—沙依拉姆断裂库仑应力最大增加量达到0.22 MPa,喀拉铁克断裂、衣木干他乌断裂、塔塔埃尔塔格断裂、奥兹格尔他乌断裂、柯坪断裂的库仑应力变化并不明显,迈丹—沙依拉姆断裂库仑应力增加最大,应注意该断层的地震活动性。

加热温度对高钒高速钢中M2C碳化物分解转变行为的影响

基于高耐磨性的需要,设计了一种W3Mo4Cr5V6高钒高速钢,利用SEM、EMPA等手段对该钢高温加热过程亚稳态M_(2)C碳化物的分解转变行为进行了分析。结果表明,共晶碳化物M_(2)C在高温加热过程会发生M_(2)C+γ-Fe→M_(6)C+MC+M_(7)C_(3)的转变,在富Mo、W的M_(2)C相周围形成了大量富W、Mo的M_(6)C及少量富V的MC和富Cr的M_(7)C_(3)。随着温度由950℃增至1150℃,M_(2)C高温转变逐渐趋于完全,且纤维状M_(2)C比层片状M_(2)C更易分解转变,最终,由呈断续网状分布于奥氏体晶界的层片或纤维状形貌向零星分布于晶界的颗粒状形貌过渡,可有效减少网状碳化物对晶界的危害。研究可为高速钢中晶界碳化物成分、形态控制及其热加工、热处理过程温度与时间等参数选择提供有效参考。

m5C甲基化修饰及其在肿瘤免疫治疗中的研究进展

表观遗传修饰在真核细胞生物学过程中有重要的调节作用。肿瘤免疫疗法是治疗癌症的重要手段和临床策略。5⁃甲基胞嘧啶(5⁃methylcytosine,m5C)是继N6甲基腺苷(N6⁃methyladenosine,m6A)之后发现的表观遗传调控网络的重要组成部分。RNA的m5C甲基化修饰能影响被修饰RNA分子的命运,并在包括RNA稳定性、蛋白质合成和转录调控在内的各种生物学过程中发挥重要作用。最近研究表明,m5C甲基转移酶、去甲基化酶、甲基化识别蛋白与多种细胞生物学过程和系统性疾病有关,包括肿瘤的发生、转移和肿瘤免疫微环境等。m5C甲基化修饰可在多个水平上广泛影响基因表达和肿瘤发生发展的生物学过程,但其具体机制及与其他表观遗传修饰的相互作用尚未阐明,其在恶性肿瘤中的调控机制、风险评估和靶向治疗的研究有待深入。本文将从m5C的动态调节网络、m5C修饰在实体瘤中的生物学作用及在肿瘤免疫治疗中的潜在靶点等进行综述。

基于m5C相关基因构建三阴性乳腺癌预后预测模型及药物敏感性分析

为了探讨5-甲基胞嘧啶(5-methylcytosine,m5C)相关基因在三阴性乳腺癌(triple negative breast cancer,TNBC)患者治疗及预后中的潜在价值,构建了基于m5C相关基因的预后预测模型,用于评估TNBC患者的预后和生存状况。从基因表达总库(gene expression omnibus,GEO)数据库和癌症基因组图谱(the cancer genome atlas,TCGA)数据库中下载TNBC基因表达谱和相应的临床数据。通过Pearson分析确定了99个m5C相关基因,进一步采用单因素Cox分析鉴定出5个与预后有关的m5C相关基因(SLC6A14、BCL11A、UGT8、LMO4、PSAT1)并构建了风险评分(risk score)预测模型,根据风险评分中位值将患者划分为高风险组和低风险组。使用Kaplan-Meier(K-M)生存分析、受试者工作特征(receiver operating characteristic,ROC)曲线、多变量Cox回归分析、构建列线图和校准曲线评估了模型的预测效能。训练集和验证集的K-M生存曲线、受试者工作特征曲线下面积(area under the curve,AUC)分析均验证了模型具有良好的预测能力。多变量Cox回归分析显示,风险评分可作为独立的预后生物标志物。使用ssGSEA、免疫评分分析和化疗药物对高低风险组患者的半最大抑制浓度(half maximal inhibitory concentration,IC50)值差异分析显示,免疫细胞和免疫检查点基因以及大多数化疗药物的IC50值在不同风险组之间的表达存在显著差异。研究结果构建了基于5个m5C相关基因的风险评分预后预测模型,这将有助于阐明TNBC中m5C相关基因的作用机制,进而提供更有价值的预后及诊断的生物标志物和潜在的治疗靶点,为TNBC患者临床个性化治疗提供理论指导。