粒细胞样髓源性抑制细胞在非小细胞肺癌中的研究进展

粒细胞样髓源性抑制细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)是MDSCs的主要亚群之一,在多数癌症中广泛富集,通过表达精氨酸酶1(arginase-1,Arg-1)及活性氧(reactive oxygen species,ROS)等机制抑制淋巴T细胞杀伤功能,重塑肿瘤免疫微环境,促进肿瘤的发生发展。近年来,越来越多的研究发现G-MDSCs与非小细胞肺癌患者的预后和免疫治疗疗效具有显著相关性,使用特异性靶向G-MDSCs的募集、分化和功能的药物能够有效抑制肿瘤的进展。本文主要就G-MDSCs在非小细胞肺癌中的免疫抑制作用及其相关通路靶向药物的研究进展进行综述。

金属镍活性中心在惰性金属载体中的自分散及其催化炔烃选择加氢性能

单位点催化剂因具有较好的活性、较高的原子利用率和目标产物选择性,在基础科学研究及工业生产领域受到了广泛关注.然而,单位点催化剂的合成策略通常较为繁琐,需要精细调控金属活性中心与载体之间的相互作用.较弱的相互作用可能会导致金属活性位点的迁移和聚集,形成金属团簇,进而引发不必要的副反应.另一方面,过分紧密的相互作用可能会限制金属活性位点的原子效率,从而降低反应活性.本文开发了一种简单通用的自分散策略,用于制备金属态单位点催化剂.该方法利用过渡金属活性中心镍在惰性载体(铝和镁)中的自分散行为,成功构筑了含有孤立过渡金属镍活性中心的全金属催化体系.X射线光电子能谱、低能离子散射和球差矫正扫描透射电子显微镜等表征结果证实了镍/铝催化剂中镍物种以金属态存在,且以孤立状态均匀分布于铝基载体的亚表层.在气固相乙炔选择加氢反应中,镍/铝和镍/镁催化剂表现出较好的催化性能,能够实现100%的乙炔转化率和高乙烯选择性.值得注意的是,镍/铝催化剂在碳碳三键选择加氢反应中的催化性能甚至超越了工业界广泛使用的林德拉催化剂.稳定性测试结果表明,镍/铝催化剂在长达90 h的连续反应中,能够维持稳定的乙炔转化率和乙烯选择性,没有明显的活性下降,进一步印证了其在工业应用中的潜在价值.结合动力学分析、原位红外光谱、氢-氘-乙炔脉冲响应实验以及理论计算等结果,详细阐释了镍/铝催化体系上乙炔选择加氢的反应机制.结果表明,氢气分子优先在镍/铝催化剂表面吸附并发生解离,生成氢原子,随后与乙炔分子逐步反应生成乙烯.在该过程中,氢气的解离活化是整个反应过程的决速步.此外,还进一步探讨了镍/铝催化体系对液相炔烃、炔醇选择加氢的性能,发现该催化剂可以在较为温和的条件下高效催化不同官能团修饰的炔烃、炔醇的选择加氢反应,同时保持高底物转化率和较好的烯烃、烯醇选择性,且表现出较好的循环稳定性.综上所述,本文发展了一种全金属单位点催化体系的通用构筑策略,不仅扩展了单位点金属催化体系的合成方法,同时利用全金属体系的本征优势,为化学转化反应过程提供了新的思路.上述发现为设计合成新型高效催化体系提供了重要的理论和实验依据,有望在精细化学品合成工业中得到应用.

EGFR-TKIs与二甲双胍联合治疗在非小细胞肺癌EGFR-TKIs获得性耐药中的研究进展

靶向表皮生长因子受体(epidermal growth factor receptor, EGFR)的EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors, EGFR-TKIs)对EGFR突变阳性的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者具有较好的疗效,但是会不可避免地出现耐药问题。随着个体化和联合治疗的应用和拓展,越来越多的研究显示二甲双胍联合给药在临床治疗中有效解决了EGFR-TKIs获得性耐药的难题,并延长了NSCLC患者的生存期。EGFR-TKIs联合二甲双胍有望成为NSCLC患者出现EGFR-TKIs耐药后可选择的治疗方法,本文拟对EGFR-TKIs与二甲双胍联合治疗NSCLC EGFR-TKIs获得性耐药中的研究进展进行总结,以期为出现EGFR-TKIs获得性耐药的NSCLC患者的治疗提供新的思路。

NMR diffusion analysis of catalytic conversion mixtures from lignocellulose biomass using PSYCHE-iDOSY

The component analysis and structure characterization of complex mixtures of biomass conversion remain a challenging work.Hence,developing effective and easy to use techniques is necessary.Diffusion-ordered NMR spectroscopy(DOSY)is a non-selective and non-invasive method capable of achieving pseudo-separation and structure assignments of individual compounds from biomass mixtures by providing diffusion coefficients(D)of the components.However,the conventional 1H DOSY NMR is limited by crowded resonances when analyzing complex mixtures containing similar chemical structure resulting in similar coefficient.Herein we describe the application of an advanced diffusion NMR method,Pure Shift Yielded by CHirp Excitation DOSY(PSYCHE-iDOSY),which can record high-resolution signal diffusion spectra efficiently separating compounds in model and genuine mixture samples from cellulose,hemicellulose and lignin.Complicated sets of isomers(D-glucose/D-fructose/D-mannose and 1,2-/1,5-pentadiol),homologous compounds(ethylene glycol and 1,2-propylene glycol),model compounds of lignin,and a genuine reaction system(furfuryl alcohol hydrogenolysis with ring opening)were successfully separated in the diffusion dimension.The results show that the ultrahigh-resolution DOSY technique is capable of detecting and pseudo-separating the mixture components of C_(5)/C_(6) sugar conversion products and its derivative hydrogenation/hydrogenolysis from lignocellulose biomass.

Insights into electrochemical CO_2 reduction on tin oxides from first-principles calculations

Density functional theory calculations were used to unravel the mechanism of CO_2 electroreduction on SnO_x surfaces. Under highly reducing conditions(<-0.6 V vs. RHE), the SnO(101) surface with oxygen vacancies is likely the active phase for CO_2 reduction. We showed that the proton-electron transfer to adsorbed *CO_2 forming *OCHO, a key intermediate for producing HCOOH, is energetically more favorable than the formation of *COOH, justifying the selectivity trends observed on Sn-based electrocatalysts. With linear scaling relations, we propose the free formation energy of *CO_2 at the oxygen vacancy as the reactivity descriptor. By engineering the strain of the SnO(101) surface, the selectivity towards HCOOH can be further optimized at reduced overpotentials.

Encapsulated Fe(IV)Molecular Complex for Photoacoustic Imaging

stable neutral Fe(IV)complex(Fe-HDCL),readily accessible on the g scale,was found to possess high water solubility and good stability(<5%degradation over 4 h upon photoirradiation).Fe-HDCL is green and absorbs light effectively in the visible region(500–800 nm)with aλmax at 650 nm(ɛ=7830 M^(−1)cm^(−1)).Fe-HDCL also exhibits photothermal(PT)behavior comparable to single-wall carbon nanotubes in the solid state.In aqueous solution,high PT conversion(η=72.6%)is achieved,and a strong hyperthermia-based inhibition of cell growth is observed upon subjecting Fe-HDCL to near-infrared 730 nm laser photoirradiation.Initial biological studies in vitro and in vivo confirmed that Fe-HDCL is biocompatible,clears readily,and allows the visual detection of blood vessels.Upon subjecting mice to intravenous injection at low doses(e.g.,50μmol·kg^(−1)),Fe-HDCL also permits the photoacoustic(PA)imaging of kidneys and the evaluation of renal fibrosis in mouse models.In addition,Fe-HDCL allows PA-based imaging of brain tissues,presumably reflecting its ability to pass through the blood-brain barrier.We thus propose that Fe-HDCL has a role to play as PT agent and as a photodiagnostic.

Effect of exogenous additives on heavy metal passivation and nitrogen retention in pig manure composting

The widespread use of feed additives in intensive and large-scale pig farming has resulted in high levels of heavy metals in pig manure.The long-term application of organic fertilizers containing high levels of heavy metals leads to the accumulation of heavy metals in the soil,which not only causes heavy metal pollution in the soil,and also affect food safety and endanger human health.Composting is an economical and effective technical measures to achieve environmentally-sustainable treatment of pig manure and is a practical method to reduce the problem of heavy metals and to improve the resource value of pig manure.The composting process is accompanied by high temperatures and the production and emission of gases,and also lead to changes in the nitrogen content of the compost and provide opportunity for heavy metal passivation additives.This paper summarizes the forms and types of heavy metals present in pig manure and reviews the progress of research as well as the techniques and problems of in the composting process,and provides recommendations for research on heavy metal passivation and nitrogen retention in pig manure composting.

Cesium-rubidium mineralization in Himalayan leucogranites

This paper presents a study of a newly discovered pollucite-lepidolite-albite granite(PLAG)in the Himalayan leucogranite belt,which marks the first occurrence of pollucite,a major cesium silicate mineral,in the Himalayan orogenic belt(China).The rock appears at the northern part of the Gyirong pluton,coexisting with the tourmaline-bearing two-mica granite(TMG).Primary rare-metal minerals include lepidolite(Li),spodumene(Li),pollucite(Cs),cassiterite(Sn),and microlite(Ta).Micas,mainly lithian muscovite to lepidolite,contain 4.07 wt.%Li_2O and 0.76 wt.%Rb_2O on average.The average Li_2O content of the spodumene is 7.95 wt.%.Pollucite not only has an average Cs_2O content of 34 wt.%,but also has an elevated Rb_2O content of about 0.16 wt.%.Notably,this granite attains industrial grades for rare metals,specifically with Li_2O,Rb_2O,and Cs_2O contents of 0.49–1.19 wt.%,0.12–0.24 wt.%,and 0.69–2.33 wt.%,respectively.Dating results of magmatic accessory cassiterite and monazite indicated that the PLAG was formed at 19–18 Ma,slightly later than the TMG(22–20 Ma)of the Gyirong pluton.Thus,these two types of granites may form within the same magmatic system considering their pulsating intrusive contact,formation ages,and whole-rock and mineral chemical compositions.Furthermore,the abundant presence of pollucite suggests that the PLAG experienced high degrees of magmatic fractionation.In comparison to the Pusila spodumene pegmatite in the Himalaya and the Yashan topaz-lepidolite granite in Jiangxi,South China,the Gyirong PLAG exhibits different whole-rock and mineral compositions,resulting from differences in source materials and fractionation processes.Notably,the difference in fluorine(F)content may determine the degree of rare-metal element enrichment.The discovery of Gyirong PLAG highlights multiple stages and types of rare-metal mineralization in the Himalayan leucogranite belt,which is controlled by the South Tibetan Detachment System.The Cs-bearing geyserite deposit exposed along the Yarlung-Zangbo River,together with Himalayan leucogranites,constitutes two systems of rare-metal elements migration and enrichment.These two systems reflect the interaction among Earth systems across time and space,emphasizing how the Himalayan orogeny controls mineralization.As a result,the Himalayan leucogranite belt has considerable prospecting potential for cesium and rubidium resources and may be a crucial area for future exploration and resource utilization.

Dynamic modeling of tectonic carbon processes:State of the art and conceptual workflow

Plate tectonics plays a critical role in modulating atmospheric CO_(2)concentration on the geological timescale(≥106year).A growing consensus on tectonic and Earth’s CO_(2)history in the Cenozoic and deeper time provides solid restrictions and standards for testing tectonic carbon processes against global measurements.Despite this,modeling the causal relationship between tectonic events and atmospheric CO_(2)levels remains a challenge.We examine the current state of the global tectonic CO_(2)research and suggest a conceptual workflow for numerical experiments that integrates plate tectonics and deep carbon dynamics.Future tectonic carbon cycle modeling should include at least four modules:(1)simulation of carbon-carrying processes,such as carbon ingassing and outgassing at the scale of minerals;(2)calculation of CO_(2)fluxes in tectonic settings like subduction,mantle plume,and plate rifting;(3)reconstruction of carbon cycling within the plates-scale tectonic scenario,particularly involving the processes of supercontinent convergence and dispersion;and(4)comparison with atmospheric CO_(2)history data and iterations,aiming to find the coincidental link between different tectonic carbon fluxes and climate changes.According to our analysis,the recent advancements in each of the four modules have paved the path for a more general assembly.We envision that the large variety of carbon transportation parameters across more than ten orders of magnitude in both time and space is the primary technical hurdle in simulating tectonic carbon dynamics.We propose a boundary-condition-connected approach for simulating the global carbon cycle to realize carbon exchange between the solid earth and surface spheres.

Three Gorges Dam:the changing trend of snail density in the Yangtze River basin between 1990 and 2019

Background The area of Oncomelania hupensis snail remains around 3.6 billion m^(2),with newly emerging and reemergent habitats continuing to appear in recent years.This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam(TGD).Methods Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance.Meta-analysis was conducted to estimate the snail density.Joinpoint model was used to identify the changing trend and inflection point.Inverse distance weighted interpolation(IDW)was used to determine the spatial distribution of recent snail density.Results A total of 3777 snail survey sites with a precise location of village or beach were identified.For the downstream area,snail density peaked in 1998(1.635/0.11 m^(2),95%CI:1.220,2.189)and fluctuated at a relatively high level before 2003,then declined steadily from 2003 to 2012.Snail density maintained lower than 0.150/0.11 m^(2) between 2012 and 2019.Joinpoint model identified the inflection of 2003,and a significant decreasing trend from 2003 to 2012 with an annual percentage change(APC)being−20.56%(95%CI:−24.15,−16.80).For the upstream area,snail density peaked in 2005(0.760/0.11 m^(2),95%CI:0.479,1.207)and was generally greater than 0.300/0.11 m2 before 2005.Snail density was generally lower than 0.150/0.11 m^(2) after 2011.Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being−6.05%(95%CI:−7.97,−7.09),and no inflection was identified.IDW showed the areas with a high snail density existed in Poyang Lake,Dongting Lake,Jianghan Plain,and the Anhui branch of the Yangtze River between 2015 and 2019.Conclusions Snail density exhibited a fluctuating downward trend in the Yangtze River basin.In the downstream area,the operation of TGD accelerated the decline of snail density during the first decade period,then snail density fluctuated at a relatively low level.There still exists local areas with a high snail density.Long-term control and monitoring of snails need to be insisted on and strengthened.

Deterioration of equivalent thermal conductivity of granite subjected to heating-cooling treatment

Understanding the thermal conductivity of granite is critical for many geological and deep engineering applications.The heated granite was subjected to air-,water-,and liquid nitrogen(LN2-)coolings in this context.The transient hot-wire technique was used to determine the equivalent thermal conductivity(ETC)of the granite before and after treatment.The deterioration mechanism of ETC is analyzed from the meso-perspective.Finally,the numerical model is used to quantitatively study the impact of cooling rate on the microcrack propagation and heat conduction characteristics of granite.The results show that the ETC of granite is not only related to the heating temperature,but also affected by the cooling rate.The ETC of granite decreases nonlinearly with increasing heating temperature.A faster cooling rate causes a greater decrease in ETC at the same heating temperature.The higher the heating temperature,the stronger the influence of cooling rate on ETC.The main explanation for the decrease in ETC of granite is the increase in porosity and microcrack density produced by the formation and propagation of pore structure and microcracks during heating and cooling.Further analysis displays that the damage of granite at the heating stage is induced by the difference in thermal expansion and elastic properties of mineral particles.At the cooling stage,the faster cooling rate causes a higher temperature gradient,which in turn produces greater thermal stress.As a result,it not only causes new cracks in the granite,but also aggravates the damage at the heating stage,which induces a further decrease in the heat conduction performance of granite,and this scenario is more obvious at higher temperatures.

Rapid denudation of the Himalayan orogen in the Nyalam area,southern Tibet, since the Pliocene and implications for tectonics–climate coupling

The Himalayan orogen characterized by very high variability in tectonic and climatic processes,and is thus regarded as a natural laboratory for investigating the coupling of tectonics and climate,as well as the influence of this coupling on geomorphological processes.This study uses apatite fission track(AFT)dating of samples from a45-km-long section crossing the Great Himalaya Crystalline Complex(GHC)in the Nyalam area,southern Tibet,to constrain the timing and rate of late Cenozoic denudation.The AFT ages can be divided into two groups:(1)15–6 Ma,to the north of Nyalam town,for which the bestfit line of elevation-age has a gentle slope of 0.05,and for which a denudation rate of 0.27 mm/a is calculated;and(2)3–1 Ma,south of Nyalam town,for which the best-fit line has a steep slope of 0.64,and for which a denudation rate of 1.32 mm/a is calculated.The whole AFT ages has a positive correlation with sample elevation(i.e.,older ages are found at higher elevations),and the geographical location of the point of inflexion of the two fitted lines corresponds closely to the junction of Poqu River near Nyalam town.By integrating the AFT data with thermotectonic modeling,it can be inferred that the GHC has experienced two different periods of denudation:(1)slow denudation during middle to late Miocene(15–6 Ma)is recorded in the northern part of the GHC;and(2)rapid denudation from the Pliocene to the Pleistocene(3–1 Ma)is recorded in the southern part of the GHC.An abrupt change in denudation rate occurred between the two periods,with the Pliocene–Pleistocene denudation rate being five times higher than that during the Miocene.This abrupt change in denudation rate during Pliocene pervaded the Himalayan orogen,and was roughly synchronous with a marked change in global climate at 4–3 Ma,and intensification of the Asian monsoon.Importantly,the later period of rapid denudation in the study region closely coupled to the mean annual precipitation,while there is no clear evidence for large-scale faulting activity and associated uplift during this period.Therefore,climate(precipitation)is inferred to be the main cause of the rapid denudation of the Himalayan orogen since the Pliocene.

Chemistry,Biosynthesis,and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery.The unique marine environment brings us a large group of halogen-containing natural products with abundant biological functionality and good drugability.Meanwhile,biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds.Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years,it is necessary to summarize these compounds with their diverse structures and promising bioactivities.In this review,we have summarized the chemistry,biosynthesis(related halogenases),and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021.Those reviewed chlorinated and brominated compounds with the ratio of 9:1 were predominantly originated from 36 genera of fungi(62%)and 9 bacterial strains(38%)with cytotoxic,antibacterial,and enzyme inhibitory activities,structural types of which are polyketides(38%),alkaloids(27%),phenols(11%),and others.This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.

Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity

Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.

Sulfate Binding with a Tripodal Tris（4-pyridylurea） Receptor

The tris（2-aminoethyl）amine （tren）-based tris（4-pyridylurea） receptor L has been synthesized and its anion binding properties were studied. The ligand forms a 2 ： 1 （host/guest） complex with MgSO4, [SO4^2 L2], in which a sulfate ion is encapsulated by six urea groups from the two ligands through multiple hydrogen bonds. The metal ions do not coordinate to the pyridyl groups but exist as the hydrate [Mg（H2O）6]2＋ and interact with the [SO4 L2] capsules in the outer coordination sphere to form a three dimensional extended structure. The anion binding behav- ior of ligand L in solution was studied.

Elastic organic crystals with ultralong phosphorescence for flexible anti-counterfeiting

Ultralong organic phosphorescence(UOP)crystals have attracted increased attention due to the distinct photophysical property of a long-lived lifetime.However,organic crystals are generally brittle,leading to a serious problem for their application in flexible technology.Herein,we report three types of elastic organic crystals(EOCs)with ultralong phosphorescence via introducing halogen atoms(Cl,Br,I)intoπ-conjugated phosphorescent molecules.Especially,the crystal containing iodine atoms displayed both excellent elasticity(ε=3.01%)and high phosphorescent efficiency(Φ_(Ph)=19.1%)owing to the strong halogen bonds.Taking advantage of its highly efficient UOP and excellent elasticity,we successfully used a DCz4I crystal for anti-counterfeiting application.These findings may provide guidance for the development of elastic crystals with afterglow and expand the scope of potential applications on flexible materials.

Characteristics of Lung Function and Prevalence of Airflow Obstruction Among Individuals Aged 18–74 Years-Beijing,China,2017–2018

What is already known about this topic?Airflow obstruction is the hallmark of many chronic respiratory diseases and may indicate the potential for the development of other progressive diseases.There are currently no representative studies of lung function in Beijing.An up-to-date estimation of the characteristics of lung function and airflow obstruction is thus needed.What is added by this report?The estimated prevalence of airflow obstruction was 14.68%in Beijing,2017–2018.The values of vital capacity,forced vital capacity,and forced expiratory volume in the first second were 3.09 L,2.66 L,2.22 L,respectively.What are the implications for public health practice?Effective public health strategy for lung in Beijing should target older people,current or former smokers,and individuals who live in urban environments,have a low education level,exhibit a high smoking index,and/or have an abnormal body mass index.