联合免疫检查点抑制剂治疗驱动基因阴性非小细胞肺癌脑转移的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌中最常见的组织学类型,约66%的患者在确诊时就被发现伴有远处转移。脑转移是最常见的转移部位之一,约13%的患者在初诊时即发现颅内受累,严重影响生活质量,预后不佳。驱动基因阳性的NSCLC脑转移患者靶向治疗可以达到较好的颅内控制率,但驱动基因阴性的患者治疗手段较为局限。近年来,随着免疫治疗的兴起,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)被广泛运用于临床,ICIs联合放疗的治疗模式为驱动基因阴性NSCLC脑转移患者的治疗带来了新希望。本文就放疗联合免疫治疗在敏感驱动基因阴性NSCLC脑转移患者中的临床研究进展进行综述,以期为临床治疗方案的选择提供参考。

Dietary L-arginine supplementation reduces lipid accretion by regulating fatty acid metabolism in Nile tilapia(Oreochromis niloticus)

Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.

The Climate Change in Qingdao during 1899-2015 and Its Response to Global Warming

In this work, the average mean (TAvg), maximum (TMax), and minimum temperature (TMin) and precipitation records of Qingdao from 1899 to 2015 are analyzed. The TAvg, TMax and TMin all go through several warm and cold periods, and exhibit statistically significant linear warming trend especially in spring and winter, as a response to global warming. Besides, the TAvg reflects more the TMin evolution for the most part, either as a trend or an abrupt change, and the contribution of TMin to Tavg is far greater than that of TMax. The abrupt change year of climate is also around 1979 in Qingdao, and it is 2 or 3-years later than the TAvg for the TMin, while there is no abrupt change of TMax. In terms of the precipitation in Qingdao, it varies periodically and dramatically with a slow increasing trend. As for the seasonal precipitation, the precipitation varies widely year by year for the four seasons but with no obvious variation trend except for spring.

Comprehensive Grain Potential Regionalization Study Based on the Farmland Grading Results

To find out the spatial pattern of comprehensive grain potential,we chose α,R i,Y i from the research output of farmland grading and took them as the basic data; using the Aggregated Advantage Indices and hierarchical cluster analysis methods,finally regionalized all the12 counties into 4 regions: I High potential-regions easy to be mined in the short term,II High potential-regions that can be mined in the long term,III Low potential-regions easy to be mined in the short term,IV Low potential-regions difficult to be mined in the long term. From the study results,we also find out that the Scale Advantage Indices of farmland( SAI) has a strong positive effect on the Aggregated Advantage Indices of grain potential( AAI),so we conclude that it is necessary to maintain and increase a certain amount of farmland area to ensure the regional grain production capacity.

Harnessing bacteria for tumor therapy:Current advances and challenges

After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treatments.Obligate and facultative anaerobes with active tropism can selectively colonize at tumor sites and suppress tumor growth via different mechanisms,serving as attractive tools for tumor treatment either as a monotherapy or combining with other therapies for synergistic anti-tumor effects.In this critical review,we introduce the recent advances of bacteria-based tumor therapy from the following aspects.First,the general properties of bacteria are reviewed emphasizing on their structural components related to tumor immunotherapy,and the main bacteria that have been used in tumor therapy are listed.Then,the benefits of bacteria for tumor therapy are illustrated,such as tumor targetability,deep penetration,and facile genetic engineering for attenuation,enhanced efficacy,as well as bioimaging.Next,anti-tumor mechanisms of bacteria are summarized,which refer to intrinsic tumoricidal activities,immune activation,bacteria metabolism,and their capability to regulate gut microbiota homeostasis.Moreover,bacteria could act as carriers to deliver various types of therapeutics to achieve combination therapy with improved efficacy.In addition,several challenges for anti-tumor applications of bacteria are discussed regarding the delivery,efficacy and safety issues,and potential solutions are also provided.Finally,the possible improvements and perspectives are discussed in the end,which provide a guideline for the design of advanced bacteria-based tumor therapeutics in the future.

Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy.However,its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment(ITM).Here,we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate(CaCO_(3))biomineralized Salmonella(Sal)as an in-situ cancer vaccine producer and systematical ITM regulator.CaCO_(3) can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading,and such biomineralization did not affect the bioactivities of the bacteria.Upon intratumoral accumulation,the CaCO_(3) shell was decomposed at an acidic microenvironment to atenuate tumor acidity,accompanied by the release of Sal and Ca^(2+)/A23187.Specifically,Sal served as a cancer vaccine producer by inducing cancer cells'immunogenic cell death(ICD)and promoting the gap junction formation between tumor cells and dendritic cells(DCs)to promote antigen presentation.Ca^(2+),on the other hand,was intermalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system,including DCs maturation,macrophages polarization,and T cells activation.As a result,such bio-vaccine achieved remarkable effcacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility.This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

Synergistic effect of F and triggered oxygen vacancies over F-TiO_(2) on enhancing NO ozonation

Oxidation-absorption technology is a key step for NOxremoval from low-temperature gas.Under the condition of low O_(3)concentration(O_(3)/NO molar ratio = 0.6), F-TiO_(2)(F-TiO_(2)), which is cheap and environmentally friendly, has been prepared as ozonation catalysts for NO oxidation. Catalytic activity tests performed at 120℃showed that the NO oxidation efficiency of F-TiO_(2)samples was higher than that of TiO_(2)(about 43.7%), and the NO oxidation efficiency of F-TiO_(2)-0.15 was the highest, which was 65.3%. Combined with physicochemical characteristics of catalysts and the analysis of active species, it was found that there was a synergistic effect between F sites and oxygen vacancies on F-TiO_(2), which could accelerate the transformation of monomolecular O_(3)into multi-molecule singlet oxygen(1O_(2)), thus promoting the selective oxidation of NO to NO_(2). The oxidation reaction of NO on F-TiO_(2)-0.15 follows the Eley-Rideal mechanism, that is, gaseous NO reacts with adsorbed O_(3)and finally form NO_(2).

Effect of interaction between different CeO_(2)plane and platinum nanoparticles on catalytic activity of Pt/CeO_(2)in toluene oxidation

The plane exposure of support vitally affects the catalytic performance of the catalyst.In this work,CeO_(2)nanorods((110)plane exposure),nano-octahedrons((111)plane exposure)and nano-cubes((100)plane exposure)were prepared as the supports of Pt/CeO_(2)samples to investigate the effect of CeO_(2)plane exposure on total toluene oxidation.Characterizations reveal that the(110)plane of CeO_(2)is more helpful to the dispersion of Pt species,followed by(111)face.The improved dispersion of Pt species can enhance the metal-supports interaction,which promotes the electron transfer of CeO_(2)carrier to Pt nanoparticles and the adsorption-activation of O_(2),thereby facilitating the total oxidation of toluene via the Langmuir-Hinshelwood(L-H)mechanism.Therefore,Pt/CeO_(2)-r(nanorods)sample expresses excellent catalytic performance of toluene oxidation.Finally,the procedure of toluene total oxidation was studied by in-situ diffuse reflectance infrared Fourier transform(DRIFT)spectroscopy.We expect that this work can contribute to the development of an effective sample for the decomposition of volatile organic compounds(VOCs).

FURTHER RESEARCH OF A NEW KIND OF SERIES REPAIRABLE SYSTEM

这篇论文被奉献给学习系统的唯一和存在由使用 C 0-semigroup 理论并且由分析讨论它的指数的稳定性的动态答案光谱系统操作员和它的伪紧密的分发。一些主要可靠性索引与系统操作员和最佳的假期时间的特徵函数被讨论得到最大的系统利润在纸的结束被分析。

Karstification characteristics of the Cenomanian-Turonian Mishrif Formation in the Missan Oil Fields,southeastern Iraq,and their effects on reservoirs

The Middle Cretaceous Mishrif Formation of the Cenomanian-Turonian age is an important Middle Eastern reservoir.Previous studies have shown that carbonates in the Mishrif Formation are affected by karstification and are concentrated at the top of the formation.However,there is a lack of systematic research on the effects of karstification on the formation’s reservoir characteristics.Based on core samples,scanning electron microscopy of thin sections,and geochemical analysis of C,O,and Sr isotopes from wells in the Missan Oil Fields,unconformity was identified at the top of the B21 subzone of the Mishrif Formation.Core and cast-thin-section observations indicate that there is a significant lithological difference above and below the unconformity,and dissolution pores and voids are well-developed beneath it.Vadose silt fills the intragranular pores and geopetal fabric is developed inside some mouldic pores beneath the unconformity surface.The isotopic values of ^(87)Sr/^(86)Sr(0.707270-0.707722)and δ^(18)O(−5.94‰—−2.32‰)suggest that the top of the B21 subzone of the Mishrif Formation has been severely affected by syngenetic karst.Karstification is the key to high-quality reservoir formation and the reservoir’s oil-bearing heterogeneity.This study will inform oil and gas exploration in the Missan Oil Fields and in other areas with similar reservoir characteristics.