Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.

利多卡因雾化吸入复合丙泊酚在小儿纤维支气管镜检查中的应用研究

目的探讨利多卡因雾化吸入复合丙泊酚在小儿纤维支气管镜检查中的作用。方法纳入80例行纤维支气管镜检查的小儿患者,采用随机数表法分为对照组和研究组。对照组予以丙泊酚静脉麻醉,研究组予以利多卡因雾化吸入复合丙泊酚静脉麻醉。对比两组患儿纤维支气管镜检查基础情况(包括检查时间、一次检查成功率和呛咳情况)和镇静满意率,记录纤维支气管镜检查前(T_(1))、检查开始即刻(T_(2))、检查开始后1 min(T_(3))、检查开始后5 min(T_(4))和检查结束即刻(T_(5))的血流动力学指标[包括心率(HR)、平均动脉压(MAP)和经皮动脉血氧饱和度(SpO_(2))]和不良反应发生率。结果研究组检查时间短于对照组[(15.14±2.03)和(18.26±2.65)min](P<0.05),呛咳评分低于对照组[(2.13±0.33)和(2.86±0.47)分](P<0.05);两组患儿一次检查成功率比较,差异无统计学意义(P>0.05);研究组镇静满意率为97.50%,明显高于对照组的80.00%,差异有统计学意义(P<0.05);两组患儿HR和MAP组间、时间和交互效应比较,差异均有统计学意义(P<0.05);两组患儿HR和MAP在T_(2)、T_(3)、T_(4)和T_(5)时点均高于T_(1)时点,且T_(4)、T_(5)时点均低于T_(2)、T_(3)时点,差异有统计学意义(P<0.05)。研究组T_(1)、T_(2)、T_(3)、T_(4)和T_(5)时点HR慢于对照组,MAP低于对照组,差异有统计学意义(P<0.05);两组患儿SpO_(2)组间、时间和交互效应比较,差异均无统计学意义(P>0.05);两组患儿不良反应发生率比较,差异无统计学意义(P>0.05)。结论使用利多卡因雾化吸入复合丙泊酚,用于小儿纤维支气管镜检查,可以缩短检查时间,减轻呛咳程度,提高镇静满意率,维持血流动力学平稳,值得应用于临床。

沙库巴曲缬沙坦对射血分数降低合并低血压心衰患者的临床疗效及安全性的影响

目的观察射血分数降低合并低血压心衰患者服用沙库巴曲缬沙坦的临床疗效及安全性。方法收集昆明市第一人民医院2020年1月2021年12月心内科诊治的射血分数降低合并低血压心衰的患者100例为研究对象。随机分为观察组与对照组各50例,2组患者均给予含利尿、β受体阻滞剂等心衰规范治疗,给予沙库巴曲缬沙坦从小剂量25~50 mg每天2次开始,根据患者耐受情况,剂量每2~4周倍增1次,直至达到维持剂量。治疗12个月后,比较2组患者治疗前后心功能LVEF、LVDd、LVDs,观察SBP、DBP、血K^(+)、血Na^(+)、CTNT、NT-proBNP水平。结果治疗后2组患者LVEF较治疗前均升高、LVDd、LVDs均有降低,2组LVEF、LVDs相比差异有统计学意义(P<0.05),LVDd差异无统计学意义(P>0.05)。2组血K^(+)、血Na^(+)、CTNT治疗后有升高,差异无统计学意义(P>0.05);NT-proBNP治疗后降低差异有统计学意义(P<0.05)。2组治疗后收缩压实验组较治疗前有升高,对照组无明显变化,差异无统计学意义(P>0.05),2组治疗后舒张压无明显变化,差异无统计学意义(P>0.05)。结论治疗HFrEF合并低血压的患者服用沙库巴曲缬沙坦能改善患者心功能、对血压无影响,具有安全性。

Potential involvement of heat shock proteins in pancreaticduodenal homeobox-1-mediated effects on the genesis of gastric cancer: A 2D gel-based proteomic study

AIM To identify functional proteins involved in pancreaticduodenal homeobox-1(PDX1)-mediated effects on gastric carcinogenesis.METHODS A PDX1-overexpressed model was established by transfecting gastric cancer cell line SGC7901 with pcDNA3.1(+)-PDX1 vector(SGC-PDX1). Transfection with empty pcDNA3.1 vector(SGC-pcDNA) served as control. Comparative protein profiles of the two groups were analyzed by two-dimensional electrophoresis basedproteomics(2 DE gel-based proteomics). The differential proteins identified by 2 DE were further validated by qRTPCR and immunoblotting. Finally, co-immunoprecipitation was used to determine any direct interactions between PDX1 and the differential proteins.RESULTS2 DE gel proteomics identified seven differential proteins in SGC-PDX1 when compared with those in SGC-pcDNA. These included four heat shock proteins(HSPs; HSP70 p1 B, HSP70 p8, HSP60, HSP27) and three other proteins(ER60, laminin receptor 1, similar to epsilon isoform of 14-3-3 protein). Immunoblotting validated the expression of the HSPs(HSP70, HSP60, HSP27). Furthermore, their expressions were lowered to 80%, 20% and 24%, respectively, in SGC-PDX1, while PDX1 exhibited a 9-fold increase, compared to SGC-pcDNA. However, qRT-PCR analysis revealed that mRNA levels of the HSP s were increased in SGC-PDX1, suggesting that the expression of the HSP s was post-translationally regulated by the PDX1 protein. Finally, co-immunoprecipitation failed to identify any direct interaction between PDX1 and HSP70 proteins.CONCLUSION This study demonstrates the potential involvement of HSPs in PDX1-mediated effects on the genesis of gastric cancer.

On a Hibernation Plankton-Nutrient Chemostat Model with Delayed Response in Growth

In this paper, a hibernation plankton-nutrient chemostat model with delayed response in growth is considered. By using the stroboscopic map and the theorem of impulsive delay differential equation, a plankton-extinction boundary periodic solution is obtained. The sufficient conditions on the permanence and globally attractive of the chemostat system are also obtained. Our main results reveal that the delayed response in growth plays an important role on the dynamical behaviors of system.

System Size Resonance Associated with Canard Phenomenon in a Biological Cell System

钙摆动上的内部噪音的影响被学习。内部噪音什么时候被考虑，被发现随机的钙摆动发生，当相应确定的动力学仅仅产出一个稳定的状态时。另外，如此的摆动的性能与系统尺寸的变化显示出二最大值，显示系统尺寸回声的出现。这行为被发现亲密地与虚报现象被连接。有趣地，最佳的系统之一与真实房间尺寸缩放匹配很好，这也被发现，并且如此的匹配对控制参数的变化柔韧。

Coherent Resonance for Rate Oscillations During CO Oxidation on Pt（110） Surfaces： Interplay Between Internal and External Noise

率摆动上的噪音的效果在磅(110 ) 表面上的公司氧化期间被调查，理论上并且数字地，由集中于内部噪音的相互影响(在里面) 由于在反应事件，和外部噪音的 stochasticity (在) 源于参数不安。表面被划分成被假定很好被混合的可变尺寸的房间，并且我们在一个单个房间内考虑行为。在噪音能导致随机的摆动的地方，注意对确定的 Hopf 分叉次于最低限度的参数区域被给予，哪个与噪音紧张的变化显示出最大值的 signal-to-noise 比率(SNR ) ，已知的同样协调的回声(CR ) 。由随机的正常理论，我们显示出那在并且在以到有效噪音的一条加权的添加剂路作出贡献导致 CR 以便 SNR 在 D-1/ 飞机显示出山脉形状 D 和 1/measures 力量在并且在分别地。它被看那为在太大(在) ， CR 行为与在(在里面) 不再存在。数字模拟与理论结果显示出好协议。

Lithium decreased NR2B tyrosine phosphorylation and interactions of NR2B and PSD-95 with Src in rat hippocampus following cerebral ischemia

Objective： To study the effects of chronic lithium on N-methyl-d-aspartate receptor subunit 2B （NR2B） tyrosine phosphorylation and the interactions of NR2B and PSD-95 with Src induced by cerebral ischemia/reperfusion （I/R）. Methods： Transient （15min） cerebral ischemia was induced by four-vessel occlusion procedure in SD rats. Immunoprecipitation （IP） and immunoblotting （IB） were performed to investigate the phosphorylation and interactions of proteins. The effects of lithium on tyrosine phosphorylation of NR2B and its interactions with PSD-95 and Src were examined. Results： Transient cerebral ischemia 15 rain followed by reperfusion 6h （I/R 6h） caused a significant increase in tyrosine phosphorylation of NR2B. Administration of LiCI for 7days before ischemia caused a profound decrease in tyrosine phosphorylation of NR2B. Similiarly. the interactions of NR2B and PSD-95 with Src were also enhanced by I/R 6h. moreover, these interactions were also inhibited by chronic lithium. Conclusion： Pretreatment with lithium decrease tyrosine phosphorylation of NR2B and interactions of NR2B and PSD-95 with Src during cerebral I/R.

The neuropeptide CGRP enters the macrophage cytosol to suppress the NLRP3 inflammasome during pulmonary infection

The NLRP3 inflammasome plays an essential role in resistance to bacterial infection. The nervous system secretes multiple neuropeptides affecting the nervous system as well as immune cells. The precise impact of the neuropeptide CGRP on NLRP3 inflammasome activation is still unclear. Here, we show that CGRP negatively regulates the antibacterial process of host cells. CGRP prevents NLRP3 inflammasome activation and reduces mature IL-1β secretion. Following NLRP3 inflammasome stimulation that triggers endosome leakage, CGRP internalized to endosomal compartments is released into the cell cytosol. Cytosolic CGRP binds directly to NLRP3 and dismantles the NLRP3-NEK7 complex, which is crucial for NLRP3 inflammasome activation. CGRP administration exacerbates bacterial infection, while the treatment with a CGRP antagonist has the opposite effect. Our study uncovers a unique role of CGRP in inhibiting inflammasome activation during infections, which might shed new light on antibacterial therapies in the future.

A Literature Review of English Learning Strategies in China

This paper makes a statistical analysis of the research on English learning strategies in 13 core journals of foreign languages in China from 2003 to 2018,mainly from the perspective of research trends,research objects,and so on.The present situation of English learning strategies is reviewed in four aspects:the content and methods of the study.It is found that the research on English learning strategies in China generally shows a dynamic upward trend,and the subjects of the study are from undergraduates to graduate students,college students and middle school students,and from non-English majors to English majors.The content of the study extends from the microscopic perspective of English learning strategies to other relevance studies,and the research methods are mainly empirical research,but less argumentative research methods.In the end,some suggestions are put forward for the research of English learning strategies in China.

准二维蓝光钙钛矿发光二极管的研究进展

蓝光钙钛矿发光二极管(PeLEDs)是钙钛矿全彩显示和白光照明技术快速发展的核心技术瓶颈。准二维钙钛矿可利用层数调控和量子限域效应实现蓝光发射,还可借助其疏水有机配体显著提升膜层和器件的稳定性,已成为钙钛矿领域的研究热点。本综述总结了准二维蓝光PeLEDs在组分工程、膜层工艺及器件优化方面的进展,分析了准二维蓝光PeLEDs面临的挑战,展望了效率提升途径,并概述了未来研究方向和解决方案。

The ex vivo and in vivo biological performances of graphene oxide and the impact of surfactant on graphene oxide's biocompatibility

Graphene oxide（GO）displays promising properties for biomedical applications including drug delivery and cancer therapeutics.However,GO exposure also raises safety concerns such as potential side effects on health.Here,the biological effects of GO suspended in phosphate buffered saline（PBS）with or without 1% nonionic surfactant Tween 80 were investigated.Based on the ex vivo experiments,Tween 80 significantly affected the interaction between GO and peripheral blood from mice.GO suspension in PBS tended to provoke the aggregation of diluted blood cells,which could be prevented by the addition of Tween 80.After intravenous administration,GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system.Nevertheless,GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80.In contrast,less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension.Organs including hearts,livers,lungs,spleens,kidneys,brains,and testes did not reveal histological alterations.The indexes of peripheral blood showed no change upon GO exposure.Our results together demonstrated that Tween 80 could greatly alter GO＇s biological performance and determine the pattern of its biodistribution in mice.

The immunostimulatory effects of retinoblastoma cell supernatant on dendritic cells

Dendritic cells （DCs） are crucial for the induction and maintenance of tumor-specific immune responses. Studies have shown that tumor-associated DCs are immunosuppressed in some human tumors. However, phenotype and function of DCs in retinoblastoma （RB） remain unclear. RB cell supernatant （RBcs） was used to treat DCs in vitro to explore the effect of RB cells on DCs. DCs were generated from peripheral blood mono- nuclear cells of healthy donors. On day 5 of culture, DCs were treated with RBcs for 24 h, and then purified using magnetic beads. The maturation of DCs was induced by TNF-a or LPS. After treatment with RBcs, expression of co-stimulatory molecules CD80 and CD86 was elevated in DCs, accompanied by increased production of IL- 12p70, TNF-a, IL-6, IL-113, and IL-8 but decreased pro- duction of IL-10. RBcs neither inhibited DC maturation nor promoted DC apoptosis. Moreover, RBcs-exposed DCs stimulated allogenetic T cell proliferation and T cell- derived cytokine production. These results indicate that RBcs can improve DCs＇ antigen presenting function and capability to activate T cells, suggesting that RB cells may have an immunostimulatory effect on DCs, and DC- based immunotherapy may be adopted in the treatment of RB.

Mesoporous carbon nanomaterials induced pulmonary surfactant inhibition,cytotoxicity,inflammation and lung fibrosis

Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials（MCNs） is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics,energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10 μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774 A.1 macrophages and lung epithelial A549 cells.Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs.Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis.Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial.

A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants

Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).

基于等几何分析的太阳帆板热结构耦合随机动力响应

航天器周期性地出入日光区和背光区,会受到太阳辐射而引起周期性热应力的影响.基于等几何分析法,研究了具有随机场参数的太阳能帆板在热结构耦合下的随机动力响应.首先基于非均匀有理B样条构造了帆板的几何模型,得到太阳能帆板的热传导微分方程和振动微分方程;利用Newmark-β法求解了热-结构耦合下的微分方程,得到结构温度场和随机动力响应;最后,研究了不同随机场参数对结构动力响应的影响.

Some selected topics on structural safety

Structural safety and reliability play an extremely important role in modern life and have been one of the hot research topics in the past decades.Due to the complexity of the problem in nature,extensive studies on structural safety are still highly needed.This thematic issue of Acta Mechanica Sinica on structural safety contains nine papers addressing a wide variety of research areas ranging from the development of the fundamental numerical method for structural analysis to the reliability assessment of structures concerned by different disciplines.

Effect of Aging on the Microstructure and Mechanical Properties of 1460 Alloy

Effects of the aging temperature on the hardening response, the tensile properties and the precipitate micro- structure evolution of 1460 alloy were studied in this work. It was found that Al3 （Sc, Zr） and δ′ （Al3Li） phases were precipitated from the matrix at the very early aging stage, while the precipitation of T1 （Al2CuLi） and θ′ （Al2Cu） was much slower than that of the δ′ phase. When aging at higher temperature （160 and 190 ℃）, the δ′, T1 and θ′ phases tended to form simultaneously and grow up very quickly. Conversely, the δ′ and θ″ （Al2Cu） phases were precipitated separately and more dispersive at lower aging temperature （130 ℃）. Taken together, the alloy aged at 160 ℃ exhibited improved mechanical properties owing to the uniform dispersion of the fine T1 precipitates.

妊娠期大气细颗粒物暴露诱导子代认知和情绪障碍

妊娠期暴露于大气细颗粒物(PM_(2.5))与各种不良的出生结局密切相关.PM_(2.5)可以通过气管滴注的暴露方式进入肺泡,继而通过肺细胞进入血液循环,穿过胎盘和胎儿血脑屏障影响子代的生长发育.本文采用质谱和三维质谱成像与分子生物学方法相结合的研究策略,对经过PM_(2.5)暴露的小鼠完整胎儿、子代海马和胎盘标本进行研究分析.研究发现PM_(2.5)暴露可以引起雌性子代海马体神经退行性变化、胎盘组织细胞结构损伤和脂质体重编程,进而影响母体-胎盘交互效应,从而导致子代行为障碍.脂质生物标志物的三维空间分布变化主要集中在胎儿脑部的背侧大脑皮层和海马形成微区,以及子代海马体和胎盘的迷宫和连接微区.我们通过对阿尔兹海默症相关的转基因小鼠模型和帕金森患者脑脊液的分析,对这些与神经退行性疾病密切相关的脂质生物标志物进行验证.本研究的多项新发现对于PM_(2.5)跨代际毒性作用靶器官的精准筛选,以及相关的神经退行性疾病的研究具有重要的指导作用.

Achieving nitritation at low temperatures using free ammonia inhibition on Nitrobacter and real-time control in an SBR treating landfill leachate

Free ammonia（FA） inhibition on nitrite-oxidized bacteria（NOB） and real-time control are used to achieve nitrogen removal from landfill leachate via nitrite pathway at low temperatures in sequencing batch reactor. The inhibition of FA on NOB activity during the aerobic period was prolonged using real-time control. The degree of nitrite accumulation was monitored along with variations of the ammonia-oxidizing bacteria and NOB population using fluorescence in situ hybridization techniques. It is demonstrated that the end-point of ammonia oxidization is detected from the on-line measured dissolved oxygen,oxidization–reduction potential, and p H signals, which could avoid the loss the FA inhibition on NOB caused by excess aeration. At low temperature（13.0–17.6°C）, the level of nitrite pathway rapidly increased from 19.8% to 90%, suggesting that nitritation was successfully started up at low temperature by applying syntrophic association of the FA inhibition and real-time control, and then this high level of nitrite pathway was stably maintained for as long as 233 days. Mechanism analysis shows that the establishment of nitritation was primarily the result of predominant ammonia-oxidizing bacteria developed in the nitrifying bacteria population compared to NOB. This was mainly due to a gradual reduction of nitrite amount that is available to provide energy for the growth of NOB,eventually leading to the elimination of NOB from the bacterial clusters in sequencing batch reactor sludge system.